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Published in: Metabolic Brain Disease 3/2014

01-09-2014 | Review Article

Interleukin 6 and cognitive dysfunction

Authors: Isabel Trapero, Omar Cauli

Published in: Metabolic Brain Disease | Issue 3/2014

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Abstract

The interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in interaction between immune and nervous system. Although IL-6 has neurotrophic properties and beneficial effects in the CNS, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. The source of the increase in peripheral IL-6 remains to be established and varies among different pathologies, but has been found to be associated with cognitive dysfunction in several pathologies. This comprehensive review provides an update summary of the studies performed in humans concerning the role of central and peripheral IL-6 in cognitive dysfunction in dementias and in other systemic diseases accompained by cognitive dysfuction such as cardiovascular, liver disease, Behçet’s disease and systemic lupus erythematosus. Further research is needed to correlate specific deficits in IL-6 and its receptors in pathologies characterized by cognitive dysfunction and to understand how systemic IL-6 affects high cerebral function in order to open new directions in pharmacological treatments that modulate IL-6 signalling.
Literature
go back to reference ACR (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599–608 ACR (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599–608
go back to reference Akaneya Y, Takahashi M, Hatanaka H (1995) Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons. Exp Neurol 136:44–52PubMed Akaneya Y, Takahashi M, Hatanaka H (1995) Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons. Exp Neurol 136:44–52PubMed
go back to reference Akman-Demir G, Serdaroglu P, Tasçi B (1999) Clinical patterns of neurological involvement in Behçet's disease: evaluation of 200 patients. The Neuro-Behçet Study Group Brain 122(Pt 11):2171–2182 Akman-Demir G, Serdaroglu P, Tasçi B (1999) Clinical patterns of neurological involvement in Behçet's disease: evaluation of 200 patients. The Neuro-Behçet Study Group Brain 122(Pt 11):2171–2182
go back to reference Akman-Demir G, Tüzün E, Içöz S et al (2008) Interleukin-6 in neuro-Behçet's disease: association with disease subsets and long-term outcome. Cytokine 44:373–376PubMed Akman-Demir G, Tüzün E, Içöz S et al (2008) Interleukin-6 in neuro-Behçet's disease: association with disease subsets and long-term outcome. Cytokine 44:373–376PubMed
go back to reference Alexander SA, Ren D, Gunn SR et al (2014) Interleukin 6 and apolipoprotein E as predictors of acute brain dysfunction and survival in critical care patients. Am J Crit Care 23:49–57PubMed Alexander SA, Ren D, Gunn SR et al (2014) Interleukin 6 and apolipoprotein E as predictors of acute brain dysfunction and survival in critical care patients. Am J Crit Care 23:49–57PubMed
go back to reference Amirzargar A, Shahram F, Nikoopour E et al (2010) Proinflammatory cytokine gene polymorphisms in Behçet's disease. Eur Cytokine Netw 21:292–296PubMed Amirzargar A, Shahram F, Nikoopour E et al (2010) Proinflammatory cytokine gene polymorphisms in Behçet's disease. Eur Cytokine Netw 21:292–296PubMed
go back to reference Amos A (2002) Remediating deficits of switching attention in patients with acquired brain injury. Brain Inj 16:407–413PubMed Amos A (2002) Remediating deficits of switching attention in patients with acquired brain injury. Brain Inj 16:407–413PubMed
go back to reference Andriambeloson E, Baillet C, Vitte P-A et al (2006) Interleukin-6 attenuates the development of experimental diabetes-related neuropathy. Neuropathology 26:32–42PubMed Andriambeloson E, Baillet C, Vitte P-A et al (2006) Interleukin-6 attenuates the development of experimental diabetes-related neuropathy. Neuropathology 26:32–42PubMed
go back to reference Angelis P, Scharf S, Mander A et al (1998) Serum interleukin-6 and interleukin-6 soluble receptor in Alzheimer's disease. Neurosci Lett 244:106–108PubMed Angelis P, Scharf S, Mander A et al (1998) Serum interleukin-6 and interleukin-6 soluble receptor in Alzheimer's disease. Neurosci Lett 244:106–108PubMed
go back to reference Arai T, Mizukami K, Sasaki M et al (1994) Clinicopathological study on a case of neuro-Behçet's disease: in special reference to MRI, SPECT and neuropathological findings. Jpn J Psychiatry Neurol 48:77–84PubMed Arai T, Mizukami K, Sasaki M et al (1994) Clinicopathological study on a case of neuro-Behçet's disease: in special reference to MRI, SPECT and neuropathological findings. Jpn J Psychiatry Neurol 48:77–84PubMed
go back to reference Barres BA, Schmid R, Sendnter M, Raff MC (1993) Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 118:283–295PubMed Barres BA, Schmid R, Sendnter M, Raff MC (1993) Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 118:283–295PubMed
go back to reference Baskys A, Cheng J-X (2012) Pharmacological prevention and treatment of vascular dementia: approaches and perspectives. Experimental Gerontology 47:887–891PubMed Baskys A, Cheng J-X (2012) Pharmacological prevention and treatment of vascular dementia: approaches and perspectives. Experimental Gerontology 47:887–891PubMed
go back to reference Bauer J, Ganter U, Strauss S et al (1992) The participation of interleukin-6 in the pathogenesis of Alzheimer's disease. Res Immunol 143:650–657PubMed Bauer J, Ganter U, Strauss S et al (1992) The participation of interleukin-6 in the pathogenesis of Alzheimer's disease. Res Immunol 143:650–657PubMed
go back to reference Berkenbosch F, Biewenga J, Brouns M et al (1992) Cytokines and inflammatory proteins in Alzheimer's disease. Res Immunol 143:657–663PubMed Berkenbosch F, Biewenga J, Brouns M et al (1992) Cytokines and inflammatory proteins in Alzheimer's disease. Res Immunol 143:657–663PubMed
go back to reference Bermejo P, Martín-Aragón S, Benedí J et al (2008) Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer's disease. Immunology Letters 117:198–202PubMed Bermejo P, Martín-Aragón S, Benedí J et al (2008) Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer's disease. Immunology Letters 117:198–202PubMed
go back to reference Biber K, Pinto-Duarte A, Wittendorp MC et al (2008) Interleukin-6 upregulates neuronal adenosine A1 receptors: implications for neuromodulation and neuroprotection. Neuropsychopharmacology 33:2237–2250PubMed Biber K, Pinto-Duarte A, Wittendorp MC et al (2008) Interleukin-6 upregulates neuronal adenosine A1 receptors: implications for neuromodulation and neuroprotection. Neuropsychopharmacology 33:2237–2250PubMed
go back to reference Blum-Degen D, Müller T, Kuhn W et al (1995) Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer“s and de novo Parkinson”s disease patients. Neurosci Lett 202:17–20PubMed Blum-Degen D, Müller T, Kuhn W et al (1995) Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer“s and de novo Parkinson”s disease patients. Neurosci Lett 202:17–20PubMed
go back to reference Borhani Haghighi A, Ittehadi H, Nikseresht AR et al (2009) CSF levels of cytokines in neuro-Behçet's disease. Clin Neurol Neurosurg 111:507–510PubMed Borhani Haghighi A, Ittehadi H, Nikseresht AR et al (2009) CSF levels of cytokines in neuro-Behçet's disease. Clin Neurol Neurosurg 111:507–510PubMed
go back to reference Borowicz LM, Goldsborough MA, Selnes OA, McKhann GM (1996) Neuropsychologic change after cardiac surgery: a critical review. J Cardiothorac Vasc Anesth 10:105–112PubMed Borowicz LM, Goldsborough MA, Selnes OA, McKhann GM (1996) Neuropsychologic change after cardiac surgery: a critical review. J Cardiothorac Vasc Anesth 10:105–112PubMed
go back to reference Boulanger MJ, Chow D-C, Brevnova EE, Garcia KC (2003) Hexameric Structure and Assembly of the Interleukin-6/IL-6 {alpha}-Receptor/gp130 Complex. Science Signaling 300:2101–2104 Boulanger MJ, Chow D-C, Brevnova EE, Garcia KC (2003) Hexameric Structure and Assembly of the Interleukin-6/IL-6 {alpha}-Receptor/gp130 Complex. Science Signaling 300:2101–2104
go back to reference Cauli O, Rodrigo R, Piedrafita B et al (2007) Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology 46:514–519PubMed Cauli O, Rodrigo R, Piedrafita B et al (2007) Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology 46:514–519PubMed
go back to reference Cavaco S, da Silva AM, Pinto P et al (2009) Cognitive functioning in Behçet's disease. Ann N Y Acad Sci 1173:217–226PubMed Cavaco S, da Silva AM, Pinto P et al (2009) Cognitive functioning in Behçet's disease. Ann N Y Acad Sci 1173:217–226PubMed
go back to reference Cercy SP, Bylsma FW (1997) Lewy bodies and progressive dementia: a critical review and meta-analysis. J Int Neuropsychol Soc 3:179–194PubMed Cercy SP, Bylsma FW (1997) Lewy bodies and progressive dementia: a critical review and meta-analysis. J Int Neuropsychol Soc 3:179–194PubMed
go back to reference Cesari M, Penninx BWJH, Pahor M et al (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59:242–248PubMed Cesari M, Penninx BWJH, Pahor M et al (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59:242–248PubMed
go back to reference Chang HK, Jang WC, Park SB et al (2005) Association between interleukin 6 gene polymorphisms and Behcet's disease in Korean people. Ann Rheum Dis 64:339–340PubMedPubMedCentral Chang HK, Jang WC, Park SB et al (2005) Association between interleukin 6 gene polymorphisms and Behcet's disease in Korean people. Ann Rheum Dis 64:339–340PubMedPubMedCentral
go back to reference Chow D-C, He X-L, Snow AL et al (2001) Structure of an Extracellular gp130 Cytokine Receptor Signaling Complex. Science Signaling 291:2150–2155 Chow D-C, He X-L, Snow AL et al (2001) Structure of an Extracellular gp130 Cytokine Receptor Signaling Complex. Science Signaling 291:2150–2155
go back to reference Chung CP, Oeser A, Solus J et al (2007) Inflammatory mechanisms affecting the lipid profile in patients with systemic lupus erythematosus. J Rheumatol 34:1849–1854PubMed Chung CP, Oeser A, Solus J et al (2007) Inflammatory mechanisms affecting the lipid profile in patients with systemic lupus erythematosus. J Rheumatol 34:1849–1854PubMed
go back to reference Cojocaru IM, Cojocaru M, Miu G, Sapira V (2011) Study of interleukin-6 production in Alzheimer's disease. Rom J Intern Med 49:55–58PubMed Cojocaru IM, Cojocaru M, Miu G, Sapira V (2011) Study of interleukin-6 production in Alzheimer's disease. Rom J Intern Med 49:55–58PubMed
go back to reference D'Arcangelo G, Tancredi V, Onofri F et al (2000) Interleukin-6 inhibits neurotransmitter release and the spread of excitation in the rat cerebral cortex. Eur J Neurosci 12:1241–1252PubMed D'Arcangelo G, Tancredi V, Onofri F et al (2000) Interleukin-6 inhibits neurotransmitter release and the spread of excitation in the rat cerebral cortex. Eur J Neurosci 12:1241–1252PubMed
go back to reference Davas EM, Tsirogianni A, Kappou I et al (1999) Serum IL-6, TNFalpha, p55 srTNFalpha, p75srTNFalpha, srIL-2alpha levels and disease activity in systemic lupus erythematosus. Clin Rheumatol 18:17–22PubMed Davas EM, Tsirogianni A, Kappou I et al (1999) Serum IL-6, TNFalpha, p55 srTNFalpha, p75srTNFalpha, srIL-2alpha levels and disease activity in systemic lupus erythematosus. Clin Rheumatol 18:17–22PubMed
go back to reference De Simoni MG, De Luigi A, Gemma L et al (1993) Modulation of systemic interleukin-6 induction by central interleukin-1. Am J Physiol 265:R739–42PubMed De Simoni MG, De Luigi A, Gemma L et al (1993) Modulation of systemic interleukin-6 induction by central interleukin-1. Am J Physiol 265:R739–42PubMed
go back to reference Dellalibera-Joviliano R, Reis Dos ML, Cunha F, De Q, Donadi EA (2003) Kinins and cytokines in plasma and cerebrospinal fluid of patients with neuropsychiatric lupus. J Rheumatol 30:485–492PubMed Dellalibera-Joviliano R, Reis Dos ML, Cunha F, De Q, Donadi EA (2003) Kinins and cytokines in plasma and cerebrospinal fluid of patients with neuropsychiatric lupus. J Rheumatol 30:485–492PubMed
go back to reference Dendorfer U, Oettgen P, Libermann TA (1994) Multiple regulatory elements in the interleukin-6 gene mediate induction by prostaglandins, cyclic AMP, and lipopolysaccharide. Mol Cell Biol 14:4443–4454PubMedPubMedCentral Dendorfer U, Oettgen P, Libermann TA (1994) Multiple regulatory elements in the interleukin-6 gene mediate induction by prostaglandins, cyclic AMP, and lipopolysaccharide. Mol Cell Biol 14:4443–4454PubMedPubMedCentral
go back to reference Di Santo E, Alonzi T, Fattori E et al (1996) Overexpression of interleukin-6 in the central nervous system of transgenic mice increases central but not systemic proinflammatory cytokine production. Brain Res 740:239–244PubMed Di Santo E, Alonzi T, Fattori E et al (1996) Overexpression of interleukin-6 in the central nervous system of transgenic mice increases central but not systemic proinflammatory cytokine production. Brain Res 740:239–244PubMed
go back to reference Dunn AJ (1992) The role of interleukin-1 and tumor necrosis factor alpha in the neurochemical and neuroendocrine responses to endotoxin. Brain Res Bull 29:807–812PubMed Dunn AJ (1992) The role of interleukin-1 and tumor necrosis factor alpha in the neurochemical and neuroendocrine responses to endotoxin. Brain Res Bull 29:807–812PubMed
go back to reference Dutra LA, Gonçalves CR, Braga-Neto P et al (2012) Atypical manifestations in Brazilian patients with neuro-Behçet's disease. J Neurol 259:1159–1165PubMed Dutra LA, Gonçalves CR, Braga-Neto P et al (2012) Atypical manifestations in Brazilian patients with neuro-Behçet's disease. J Neurol 259:1159–1165PubMed
go back to reference Economos A, Wright CB, Moon YP et al (2013) Interleukin 6 Plasma Concentration Associates with Cognitive Decline: The Northern Manhattan Study. Neuroepidemiology 40:253–259PubMedPubMedCentral Economos A, Wright CB, Moon YP et al (2013) Interleukin 6 Plasma Concentration Associates with Cognitive Decline: The Northern Manhattan Study. Neuroepidemiology 40:253–259PubMedPubMedCentral
go back to reference Egashira K (2003) Molecular mechanisms mediating inflammation in vascular disease: special reference to monocyte chemoattractant protein-1. Hypertension 41:834–841PubMed Egashira K (2003) Molecular mechanisms mediating inflammation in vascular disease: special reference to monocyte chemoattractant protein-1. Hypertension 41:834–841PubMed
go back to reference Engelhart MJ, Geerlings MI, Meijer J et al (2004) Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol 61:668–672PubMed Engelhart MJ, Geerlings MI, Meijer J et al (2004) Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch Neurol 61:668–672PubMed
go back to reference Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 51:245–270PubMed Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 51:245–270PubMed
go back to reference Fried LP, Guralnik JM (1997) Disability in older adults: evidence regarding significance, etiology, and risk. J Am Geriatr Soc 45:92–100PubMed Fried LP, Guralnik JM (1997) Disability in older adults: evidence regarding significance, etiology, and risk. J Am Geriatr Soc 45:92–100PubMed
go back to reference Gadient RA, Otten U (1994a) Identification of interleukin-6 (IL-6)-expressing neurons in the cerebellum and hippocampus of normal adult rats. Neurosci Lett 182:243–246PubMed Gadient RA, Otten U (1994a) Identification of interleukin-6 (IL-6)-expressing neurons in the cerebellum and hippocampus of normal adult rats. Neurosci Lett 182:243–246PubMed
go back to reference Gadient RA, Otten U (1993) Differential expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) mRNAs in rat hypothalamus. Neurosci Lett 153:13–16PubMed Gadient RA, Otten U (1993) Differential expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) mRNAs in rat hypothalamus. Neurosci Lett 153:13–16PubMed
go back to reference Gadient RA, Otten U (1994b) Expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) mRNAs in rat brain during postnatal development. Brain Res 637:10–14PubMed Gadient RA, Otten U (1994b) Expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) mRNAs in rat brain during postnatal development. Brain Res 637:10–14PubMed
go back to reference Gadient RA, Otten UH (1997) Interleukin-6 (IL-6)–a molecule with both beneficial and destructive potentials. Prog Neurobiol 52:379–390PubMed Gadient RA, Otten UH (1997) Interleukin-6 (IL-6)–a molecule with both beneficial and destructive potentials. Prog Neurobiol 52:379–390PubMed
go back to reference Garcia-Oscos F, Salgado H, Hall S et al (2012) The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling. Biological Psychiatry 71:574–582PubMed Garcia-Oscos F, Salgado H, Hall S et al (2012) The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling. Biological Psychiatry 71:574–582PubMed
go back to reference Gauldie J, Sauder DN, McAdam KP, Dinarello CA (1987) Purified interleukin-1 (IL-1) from human monocytes stimulates acute-phase protein synthesis by rodent hepatocytes in vitro. Immunology 60:203–207PubMedPubMedCentral Gauldie J, Sauder DN, McAdam KP, Dinarello CA (1987) Purified interleukin-1 (IL-1) from human monocytes stimulates acute-phase protein synthesis by rodent hepatocytes in vitro. Immunology 60:203–207PubMedPubMedCentral
go back to reference Girotti M, Donegan JJ, Morilak DA (2012) Influence of hypothalamic IL-6/gp130 receptor signaling on the HPA axis response to chronic stress. Psychoneuroendocrinology 38:1158–1169PubMedPubMedCentral Girotti M, Donegan JJ, Morilak DA (2012) Influence of hypothalamic IL-6/gp130 receptor signaling on the HPA axis response to chronic stress. Psychoneuroendocrinology 38:1158–1169PubMedPubMedCentral
go back to reference Goodman MN (1994) Interleukin-6 induces skeletal muscle protein breakdown in rats. Proc Soc Exp Biol Med 205:182–185PubMed Goodman MN (1994) Interleukin-6 induces skeletal muscle protein breakdown in rats. Proc Soc Exp Biol Med 205:182–185PubMed
go back to reference Gómez-Tortosa E, Gonzalo I, Fanjul S et al (2003) Cerebrospinal fluid markers in dementia with lewy bodies compared with Alzheimer disease. Arch Neurol 60:1218–1222PubMed Gómez-Tortosa E, Gonzalo I, Fanjul S et al (2003) Cerebrospinal fluid markers in dementia with lewy bodies compared with Alzheimer disease. Arch Neurol 60:1218–1222PubMed
go back to reference Gruol DL, Nelson TE (1997) Physiological and pathological roles of interleukin-6 in the central nervous system. Mol Neurobiol 15:307–339PubMed Gruol DL, Nelson TE (1997) Physiological and pathological roles of interleukin-6 in the central nervous system. Mol Neurobiol 15:307–339PubMed
go back to reference Guzmán C, Hallal-Calleros C (2010) Interleukin-6: a cytokine with a pleiotropic role in the neuroimmunoendocrine network. The Open Neuroendocrinology Journal 3:152–160 Guzmán C, Hallal-Calleros C (2010) Interleukin-6: a cytokine with a pleiotropic role in the neuroimmunoendocrine network. The Open Neuroendocrinology Journal 3:152–160
go back to reference Gündüz T, Emir Ö, Kürtüncü M et al (2012) Cognitive impairment in neuro-Behcet's disease and multiple sclerosis: a comparative study. Int J Neurosci 122:650–656PubMed Gündüz T, Emir Ö, Kürtüncü M et al (2012) Cognitive impairment in neuro-Behcet's disease and multiple sclerosis: a comparative study. Int J Neurosci 122:650–656PubMed
go back to reference Hama T, Kushima Y, Miyamoto M et al (1991) Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures. Neuroscience 40:445–452PubMed Hama T, Kushima Y, Miyamoto M et al (1991) Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures. Neuroscience 40:445–452PubMed
go back to reference Hammeke TA, Hastings JE (1988) Neuropsychologic alterations after cardiac operation. J Thorac Cardiovasc Surg 96:326–331PubMed Hammeke TA, Hastings JE (1988) Neuropsychologic alterations after cardiac operation. J Thorac Cardiovasc Surg 96:326–331PubMed
go back to reference Hampel H, Haslinger A, Scheloske M et al (2005) Pattern of interleukin-6 receptor complex immunoreactivity between cortical regions of rapid autopsy normal and Alzheimer's disease brain. Eur Arch Psychiatry Clin Neurosci 255:269–278PubMed Hampel H, Haslinger A, Scheloske M et al (2005) Pattern of interleukin-6 receptor complex immunoreactivity between cortical regions of rapid autopsy normal and Alzheimer's disease brain. Eur Arch Psychiatry Clin Neurosci 255:269–278PubMed
go back to reference Hanly JG, Cassell K, Fisk JD (1997) Cognitive function in systemic lupus erythematosus: results of a 5-year prospective study. Arthritis Rheum 40:1542–1543PubMed Hanly JG, Cassell K, Fisk JD (1997) Cognitive function in systemic lupus erythematosus: results of a 5-year prospective study. Arthritis Rheum 40:1542–1543PubMed
go back to reference Hanly JG, Su L, Omisade A et al (2012) Screening for cognitive impairment in systemic lupus erythematosus. J Rheumatol 39:1371–1377PubMed Hanly JG, Su L, Omisade A et al (2012) Screening for cognitive impairment in systemic lupus erythematosus. J Rheumatol 39:1371–1377PubMed
go back to reference Hanly JG, Urowitz MB, Sanchez-Guerrero J et al (2007) Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum 56:265–273PubMed Hanly JG, Urowitz MB, Sanchez-Guerrero J et al (2007) Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum 56:265–273PubMed
go back to reference Hay EM, Huddy A, Black D et al (1994) A prospective study of psychiatric disorder and cognitive function in systemic lupus erythematosus. Ann Rheum Dis 53:298–303PubMedPubMedCentral Hay EM, Huddy A, Black D et al (1994) A prospective study of psychiatric disorder and cognitive function in systemic lupus erythematosus. Ann Rheum Dis 53:298–303PubMedPubMedCentral
go back to reference Heinrich PC, Behrmann I, Müller-Newen G et al (1998) Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J 334(Pt 2):297–314PubMedPubMedCentral Heinrich PC, Behrmann I, Müller-Newen G et al (1998) Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J 334(Pt 2):297–314PubMedPubMedCentral
go back to reference Henriksen L, Hjelms E, Lindeburgh T (1983) Brain hyperperfusion during cardiac operations. Cerebral blood flow measured in man by intra-arterial injection of xenon 133: evidence suggestive of intraoperative microembolism. J Thorac Cardiovasc Surg 86:202–208PubMed Henriksen L, Hjelms E, Lindeburgh T (1983) Brain hyperperfusion during cardiac operations. Cerebral blood flow measured in man by intra-arterial injection of xenon 133: evidence suggestive of intraoperative microembolism. J Thorac Cardiovasc Surg 86:202–208PubMed
go back to reference Hirohata S (1996) Coping with pathological changes in nerves and blood vessels in collagen disease–CNS lupus. Nippon Naika Gakkai Zasshi 85:1816–1821PubMed Hirohata S (1996) Coping with pathological changes in nerves and blood vessels in collagen disease–CNS lupus. Nippon Naika Gakkai Zasshi 85:1816–1821PubMed
go back to reference Hirohata S, Isshi K, Oguchi H et al (1997) Cerebrospinal fluid interleukin-6 in progressive Neuro-Behçet's syndrome. Clin Immunol Immunopathol 82:12–17PubMed Hirohata S, Isshi K, Oguchi H et al (1997) Cerebrospinal fluid interleukin-6 in progressive Neuro-Behçet's syndrome. Clin Immunol Immunopathol 82:12–17PubMed
go back to reference Hirohata S, Kikuchi H (2012) Changes in biomarkers focused on differences in disease course or treatment in patients with neuro-Behçet's disease. Intern Med 51:3359–3365PubMed Hirohata S, Kikuchi H (2012) Changes in biomarkers focused on differences in disease course or treatment in patients with neuro-Behçet's disease. Intern Med 51:3359–3365PubMed
go back to reference Hirohata S, Miyamoto T (1990) Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum 33:644–649PubMed Hirohata S, Miyamoto T (1990) Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum 33:644–649PubMed
go back to reference Huell M, Strauss S, Volk B et al (1995) Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients. Acta Neuropathol 89:544–551PubMed Huell M, Strauss S, Volk B et al (1995) Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients. Acta Neuropathol 89:544–551PubMed
go back to reference Hull M, Berger M, Volk B, Bauer J (1996a) Occurrence of interleukin-6 in cortical plaques of Alzheimer's disease patients may precede transformation of diffuse into neuritic plaques. Ann N Y Acad Sci 777:205–212PubMed Hull M, Berger M, Volk B, Bauer J (1996a) Occurrence of interleukin-6 in cortical plaques of Alzheimer's disease patients may precede transformation of diffuse into neuritic plaques. Ann N Y Acad Sci 777:205–212PubMed
go back to reference Hull M, Strauss S, Berger M et al (1996b) Inflammatory mechanisms in Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci 246:124–128PubMed Hull M, Strauss S, Berger M et al (1996b) Inflammatory mechanisms in Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci 246:124–128PubMed
go back to reference Imamura K, Hishikawa N, Ono K et al (2004) Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathol 109:141–150PubMed Imamura K, Hishikawa N, Ono K et al (2004) Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathol 109:141–150PubMed
go back to reference Inaba G (1984) Revised criteria for the diagnosis of Behçet's disease. Ryumachi 24:135–141PubMed Inaba G (1984) Revised criteria for the diagnosis of Behçet's disease. Ryumachi 24:135–141PubMed
go back to reference Jain L, Sharma BC, Sharma P et al (2012) Serum endotoxin and inflammatory mediators in patients with cirrhosis and hepatic encephalopathy. Dig Liver Dis 44:1027–1031PubMed Jain L, Sharma BC, Sharma P et al (2012) Serum endotoxin and inflammatory mediators in patients with cirrhosis and hepatic encephalopathy. Dig Liver Dis 44:1027–1031PubMed
go back to reference Jellinger KA (2009) Intrathecal levels of IL-6 in Alzheimer’s disease. J Neurol 257:142–142 Jellinger KA (2009) Intrathecal levels of IL-6 in Alzheimer’s disease. J Neurol 257:142–142
go back to reference Jenny NS, French B, Arnold AM et al (2012) Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars. J Gerontol A Biol Sci Med Sci 67:970–976PubMedPubMedCentral Jenny NS, French B, Arnold AM et al (2012) Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars. J Gerontol A Biol Sci Med Sci 67:970–976PubMedPubMedCentral
go back to reference Ji R, Tian S, Lu HJ et al (2013) TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation. J Immunol 191:6165–6177PubMed Ji R, Tian S, Lu HJ et al (2013) TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation. J Immunol 191:6165–6177PubMed
go back to reference Jia JP, Meng R, Sun YX et al (2005) Cerebrospinal fluid tau, Abeta1-42 and inflammatory cytokines in patients with Alzheimer's disease and vascular dementia. Neurosci Lett 383:12–16PubMed Jia JP, Meng R, Sun YX et al (2005) Cerebrospinal fluid tau, Abeta1-42 and inflammatory cytokines in patients with Alzheimer's disease and vascular dementia. Neurosci Lett 383:12–16PubMed
go back to reference Jüttler E, Tarabin V, Schwaninger M (2002) Interleukin-6 (IL-6): a possible neuromodulator induced by neuronal activity. Neuroscientist 8:268–275PubMed Jüttler E, Tarabin V, Schwaninger M (2002) Interleukin-6 (IL-6): a possible neuromodulator induced by neuronal activity. Neuroscientist 8:268–275PubMed
go back to reference Kalman J, Juhasz A, Laird G et al (2009) Serum interleukin-6 levels correlate with the severity of dementia in Down syndrome and in Alzheimer's disease. Acta Neurol Scand 96:236–240 Kalman J, Juhasz A, Laird G et al (2009) Serum interleukin-6 levels correlate with the severity of dementia in Down syndrome and in Alzheimer's disease. Acta Neurol Scand 96:236–240
go back to reference Kalman J, Juhasz A, Laird G et al (1997) Serum interleukin-6 levels correlate with the severity of dementia in Down syndrome and in Alzheimer's disease. Acta Neurol Scand 96:236–240PubMed Kalman J, Juhasz A, Laird G et al (1997) Serum interleukin-6 levels correlate with the severity of dementia in Down syndrome and in Alzheimer's disease. Acta Neurol Scand 96:236–240PubMed
go back to reference Kálmán J, Juhász A, Bogáts G et al (2006) Elevated levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are predictors of cognitive decline. Neurochemistry International 48:177–180PubMed Kálmán J, Juhász A, Bogáts G et al (2006) Elevated levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are predictors of cognitive decline. Neurochemistry International 48:177–180PubMed
go back to reference Kent SS, Kelley KWK, Dantzer RR (1992) Effects of lipopolysaccharide on food-motivated behavior in the rat are not blocked by an interleukin-1 receptor antagonist. Neurosci Lett 145:83–86PubMed Kent SS, Kelley KWK, Dantzer RR (1992) Effects of lipopolysaccharide on food-motivated behavior in the rat are not blocked by an interleukin-1 receptor antagonist. Neurosci Lett 145:83–86PubMed
go back to reference Klein MA, Möller JC, Jones LL et al (1997) Impaired neuroglial activation in interleukin-6 deficient mice. Glia 19:227–233PubMed Klein MA, Möller JC, Jones LL et al (1997) Impaired neuroglial activation in interleukin-6 deficient mice. Glia 19:227–233PubMed
go back to reference Kopf M, Baumann H, Freer G et al (1994) Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368:339–342PubMed Kopf M, Baumann H, Freer G et al (1994) Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368:339–342PubMed
go back to reference Kossmann T, Hans V, Imhof HG et al (1996) Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes. Brain Res 713:143–152PubMed Kossmann T, Hans V, Imhof HG et al (1996) Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes. Brain Res 713:143–152PubMed
go back to reference Kozora E, Ellison MC, West S (2004) Reliability and validity of the proposed American College of Rheumatology neuropsychological battery for systemic lupus erythematosus. Arthritis Rheum 51:810–818PubMed Kozora E, Ellison MC, West S (2004) Reliability and validity of the proposed American College of Rheumatology neuropsychological battery for systemic lupus erythematosus. Arthritis Rheum 51:810–818PubMed
go back to reference Kozora E, Filley CM, Zhang L et al (2012) Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations. Lupus 21:402–411PubMed Kozora E, Filley CM, Zhang L et al (2012) Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations. Lupus 21:402–411PubMed
go back to reference Krabbe KS, Pedersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Experimental Gerontology 39:687–699PubMed Krabbe KS, Pedersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Experimental Gerontology 39:687–699PubMed
go back to reference Krabbe KS, Reichenberg A, Yirmiya R et al (2005) Low-dose endotoxemia and human neuropsychological functions. BRAIN, BEHAVIOUR, AND IMMUNITY 19:453–460 Krabbe KS, Reichenberg A, Yirmiya R et al (2005) Low-dose endotoxemia and human neuropsychological functions. BRAIN, BEHAVIOUR, AND IMMUNITY 19:453–460
go back to reference Kushima Y, Hama T, Hatanaka H (1992) Interleukin-6 as a neurotrophic factor for promoting the survival of cultured catecholaminergic neurons in a chemically defined medium from fetal and postnatal rat midbrains. Neurosci Res 13:267–280PubMed Kushima Y, Hama T, Hatanaka H (1992) Interleukin-6 as a neurotrophic factor for promoting the survival of cultured catecholaminergic neurons in a chemically defined medium from fetal and postnatal rat midbrains. Neurosci Res 13:267–280PubMed
go back to reference Kushima Y, Hatanaka H (1992) Interleukin-6 and leukemia inhibitory factor promote the survival of acetylcholinesterase-positive neurons in culture from embryonic rat spinal cord. Neurosci Lett 143:110–114PubMed Kushima Y, Hatanaka H (1992) Interleukin-6 and leukemia inhibitory factor promote the survival of acetylcholinesterase-positive neurons in culture from embryonic rat spinal cord. Neurosci Lett 143:110–114PubMed
go back to reference Lanzrein AS, Johnston CM, Perry VH et al (1998) Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and brain tissue in Alzheimer disease: interleukin-1beta, interleukin-6, interleukin-1 receptor antagonist, tumor necrosis factor-alpha, the soluble tumor necrosis factor receptors I and II, and alpha1-antichymotrypsin. Alzheimer Dis Assoc Disord 12:215–227PubMed Lanzrein AS, Johnston CM, Perry VH et al (1998) Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and brain tissue in Alzheimer disease: interleukin-1beta, interleukin-6, interleukin-1 receptor antagonist, tumor necrosis factor-alpha, the soluble tumor necrosis factor receptors I and II, and alpha1-antichymotrypsin. Alzheimer Dis Assoc Disord 12:215–227PubMed
go back to reference Licastro F, Grimaldi LME, Bonafè M et al (2003) Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain. NBA 24:921–926 Licastro F, Grimaldi LME, Bonafè M et al (2003) Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain. NBA 24:921–926
go back to reference Licastro F, Pedrini S, Caputo L et al (2000) Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain? Journal of Neuroimmunology 103:97–102PubMed Licastro F, Pedrini S, Caputo L et al (2000) Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain? Journal of Neuroimmunology 103:97–102PubMed
go back to reference Lim L, Lippe S, Silverman E (2013) Effect of autoimmune diseases on cognitive function. Handb Clin Neurol 112:1275–1283PubMed Lim L, Lippe S, Silverman E (2013) Effect of autoimmune diseases on cognitive function. Handb Clin Neurol 112:1275–1283PubMed
go back to reference Linker-Israeli M, Deans RJ, Wallace DJ et al (1991) Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis J Immunol 147:117–123 Linker-Israeli M, Deans RJ, Wallace DJ et al (1991) Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis J Immunol 147:117–123
go back to reference Luo M, Li L, Yang E-N, Cao W-K (2012) Relationship between interleukin-6 and ammonia in patients with minimal hepatic encephalopathy due to liver cirrhosis. Hepatol Res 42:1202–1210PubMed Luo M, Li L, Yang E-N, Cao W-K (2012) Relationship between interleukin-6 and ammonia in patients with minimal hepatic encephalopathy due to liver cirrhosis. Hepatol Res 42:1202–1210PubMed
go back to reference Marsland AL, Gianaros PJ, Abramowitch SM et al (2008) Interleukin-6 Covaries Inversely with Hippocampal Grey Matter Volume in Middle-Aged Adults. Biological Psychiatry 64:484–490PubMedPubMedCentral Marsland AL, Gianaros PJ, Abramowitch SM et al (2008) Interleukin-6 Covaries Inversely with Hippocampal Grey Matter Volume in Middle-Aged Adults. Biological Psychiatry 64:484–490PubMedPubMedCentral
go back to reference Martínez M, Fernández-Vivancos E, Frank A et al (2000) Increased cerebrospinal fluid fas (Apo-1) levels in Alzheimer's disease. Relationship with IL-6 concentrations. Brain Res 869:216–219PubMed Martínez M, Fernández-Vivancos E, Frank A et al (2000) Increased cerebrospinal fluid fas (Apo-1) levels in Alzheimer's disease. Relationship with IL-6 concentrations. Brain Res 869:216–219PubMed
go back to reference Mastorakos G, Ilias I (2006) Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress. Ann N Y Acad Sci 1088:373–381PubMed Mastorakos G, Ilias I (2006) Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress. Ann N Y Acad Sci 1088:373–381PubMed
go back to reference May LT, Santhanam U, Sehgal PB (1991) On the multimeric nature of natural human interleukin-6. J Biol Chem 266:9950–9955PubMed May LT, Santhanam U, Sehgal PB (1991) On the multimeric nature of natural human interleukin-6. J Biol Chem 266:9950–9955PubMed
go back to reference März P, Heese K, Hock C et al (1997) Interleukin-6 (IL-6) and soluble forms of IL-6 receptors are not altered in cerebrospinal fluid of Alzheimer's disease patients. Neurosci Lett 239:29–32PubMed März P, Heese K, Hock C et al (1997) Interleukin-6 (IL-6) and soluble forms of IL-6 receptors are not altered in cerebrospinal fluid of Alzheimer's disease patients. Neurosci Lett 239:29–32PubMed
go back to reference McKeith IG, Galasko D, Kosaka K et al (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124PubMed McKeith IG, Galasko D, Kosaka K et al (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124PubMed
go back to reference Mege JL, Dilsen N, Sanguedolce V et al (1993) Overproduction of monocyte derived tumor necrosis factor alpha, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet's disease. A comparative study with familial Mediterranean fever and healthy subjects J Rheumatol 20:1544–1549 Mege JL, Dilsen N, Sanguedolce V et al (1993) Overproduction of monocyte derived tumor necrosis factor alpha, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet's disease. A comparative study with familial Mediterranean fever and healthy subjects J Rheumatol 20:1544–1549
go back to reference Monastero R, Camarda C, Pipia C et al (2004) Cognitive impairment in Behçet's disease patients without overt neurological involvement. Journal of the Neurological Sciences 220:99–104PubMed Monastero R, Camarda C, Pipia C et al (2004) Cognitive impairment in Behçet's disease patients without overt neurological involvement. Journal of the Neurological Sciences 220:99–104PubMed
go back to reference Montagnese S, Biancardi A, Schiff S et al (2011) Different biochemical correlates for different neuropsychiatric abnormalities in patients with cirrhosis. Hepatology 53:558–566PubMed Montagnese S, Biancardi A, Schiff S et al (2011) Different biochemical correlates for different neuropsychiatric abnormalities in patients with cirrhosis. Hepatology 53:558–566PubMed
go back to reference Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302:1760–1765PubMed Monje ML, Toda H, Palmer TD (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302:1760–1765PubMed
go back to reference Montoliu C, Cauli O, Urios A et al (2011) 3-nitro-tyrosine as a peripheral biomarker of minimal hepatic encephalopathy in patients with liver cirrhosis. Am J Gastroenterol 106:1629–1637PubMed Montoliu C, Cauli O, Urios A et al (2011) 3-nitro-tyrosine as a peripheral biomarker of minimal hepatic encephalopathy in patients with liver cirrhosis. Am J Gastroenterol 106:1629–1637PubMed
go back to reference Montoliu C, Piedrafita B, Serra MA et al (2009) IL-6 and IL-18 in blood may discriminate cirrhotic patients with and without minimal hepatic encephalopathy. J Clin Gastroenterol 43:272–279PubMed Montoliu C, Piedrafita B, Serra MA et al (2009) IL-6 and IL-18 in blood may discriminate cirrhotic patients with and without minimal hepatic encephalopathy. J Clin Gastroenterol 43:272–279PubMed
go back to reference Mooijaart SP, Sattar N, Trompet S et al (2013) Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study. J Intern Med 274:77–85PubMed Mooijaart SP, Sattar N, Trompet S et al (2013) Circulating interleukin-6 concentration and cognitive decline in old age: the PROSPER study. J Intern Med 274:77–85PubMed
go back to reference Murphy PG, Grondin J, Altares M, Richardson PM (1995) Induction of interleukin-6 in axotomized sensory neurons. J Neurosci 15:5130–5138PubMed Murphy PG, Grondin J, Altares M, Richardson PM (1995) Induction of interleukin-6 in axotomized sensory neurons. J Neurosci 15:5130–5138PubMed
go back to reference Naitoh Y, Fukata J, Tominaga T et al (1988) Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats. Biochem Biophys Res Commun 155:1459–1463PubMed Naitoh Y, Fukata J, Tominaga T et al (1988) Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats. Biochem Biophys Res Commun 155:1459–1463PubMed
go back to reference Nelson TE, Netzeband JG, Gruol DL (2004) Chronic interleukin-6 exposure alters metabotropic glutamate receptor-activated calcium signalling in cerebellar Purkinje neurons. Eur J Neurosci 20:2387–2400PubMed Nelson TE, Netzeband JG, Gruol DL (2004) Chronic interleukin-6 exposure alters metabotropic glutamate receptor-activated calcium signalling in cerebellar Purkinje neurons. Eur J Neurosci 20:2387–2400PubMed
go back to reference Nybo L, Nielsen B, Pedersen BK et al (2002) Interleukin-6 release from the human brain during prolonged exercise. J Physiol (Lond) 542:991–995 Nybo L, Nielsen B, Pedersen BK et al (2002) Interleukin-6 release from the human brain during prolonged exercise. J Physiol (Lond) 542:991–995
go back to reference Oktem-Tanör O, Baykan-Kurt B, Gürvit IH et al (1999) Neuropsychological follow-up of 12 patients with neuro-Behçet disease. J Neurol 246:113–119PubMed Oktem-Tanör O, Baykan-Kurt B, Gürvit IH et al (1999) Neuropsychological follow-up of 12 patients with neuro-Behçet disease. J Neurol 246:113–119PubMed
go back to reference Peters M, Müller AM, Rose-John S (1998) Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis. Blood 92:3495–3504PubMed Peters M, Müller AM, Rose-John S (1998) Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis. Blood 92:3495–3504PubMed
go back to reference Pola R, Flex A, Gaetani E et al (2002) The −174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population. J Hum Hypertens 16:637–640PubMed Pola R, Flex A, Gaetani E et al (2002) The −174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population. J Hum Hypertens 16:637–640PubMed
go back to reference Pugsley W, Klinger L, Paschalis C et al (1994) The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 25:1393–1399PubMed Pugsley W, Klinger L, Paschalis C et al (1994) The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 25:1393–1399PubMed
go back to reference Qiu Z, Sweeney DD, Netzeband JG, Gruol DL (1998) Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons. J Neurosci 18:10445–10456PubMed Qiu Z, Sweeney DD, Netzeband JG, Gruol DL (1998) Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons. J Neurosci 18:10445–10456PubMed
go back to reference Rafnsson SB, Deary IJ, Smith FB et al (2007) Cardiovascular diseases and decline in cognitive function in an elderly community population: the Edinburgh Artery Study. Psychosom Med 69:425–434PubMed Rafnsson SB, Deary IJ, Smith FB et al (2007) Cardiovascular diseases and decline in cognitive function in an elderly community population: the Edinburgh Artery Study. Psychosom Med 69:425–434PubMed
go back to reference Rose-John S (2012) IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 8:1237–1247PubMedPubMedCentral Rose-John S (2012) IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 8:1237–1247PubMedPubMedCentral
go back to reference Rosenblat JD, Cha DS, Mansur RB, McIntyre RS (2014) Inflamed moods: A review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry 53C:23–34 Rosenblat JD, Cha DS, Mansur RB, McIntyre RS (2014) Inflamed moods: A review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry 53C:23–34
go back to reference Rothenburg LS, Herrmann N, Swardfager W et al (2010) The relationship between inflammatory markers and post stroke cognitive impairment. J Geriatr Psychiatry Neurol 23:199–205PubMed Rothenburg LS, Herrmann N, Swardfager W et al (2010) The relationship between inflammatory markers and post stroke cognitive impairment. J Geriatr Psychiatry Neurol 23:199–205PubMed
go back to reference Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behçet's disease. N Engl J Med 341:1284–1291PubMed Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behçet's disease. N Engl J Med 341:1284–1291PubMed
go back to reference Sala G, Galimberti G, Canevari C et al (2003) Peripheral cytokine release in Alzheimer patients: correlation with disease severity. Neurobiology of Aging 24:909–914PubMed Sala G, Galimberti G, Canevari C et al (2003) Peripheral cytokine release in Alzheimer patients: correlation with disease severity. Neurobiology of Aging 24:909–914PubMed
go back to reference Savageau JA, Stanton BA, Jenkins CD, Frater RW (1982) Neuropsychological dysfunction following elective cardiac operation. II A six-month reassessment J Thorac Cardiovasc Surg 84:595–600 Savageau JA, Stanton BA, Jenkins CD, Frater RW (1982) Neuropsychological dysfunction following elective cardiac operation. II A six-month reassessment J Thorac Cardiovasc Surg 84:595–600
go back to reference Sawada M, Imamura K, Nagatsu T (2006) Role of cytokines in inflammatory process in Parkinson's disease. J Neural Transm Suppl 70:373–381PubMed Sawada M, Imamura K, Nagatsu T (2006) Role of cytokines in inflammatory process in Parkinson's disease. J Neural Transm Suppl 70:373–381PubMed
go back to reference Sawada M, Suzumura A, Marunouchi T (1995) Cytokine network in the central nervous system and its roles in growth and differentiation of glial and neuronal cells. Int J Dev Neurosci 13:253–264PubMed Sawada M, Suzumura A, Marunouchi T (1995) Cytokine network in the central nervous system and its roles in growth and differentiation of glial and neuronal cells. Int J Dev Neurosci 13:253–264PubMed
go back to reference Sayinalp N, Ozcebe OI, Ozdemir O et al (1996) Cytokines in Behçet's disease. J Rheumatol 23:321–322PubMed Sayinalp N, Ozcebe OI, Ozdemir O et al (1996) Cytokines in Behçet's disease. J Rheumatol 23:321–322PubMed
go back to reference Sánchez-López F, Tasset I, Agüera E et al (2012) Oxidative stress and inflammation biomarkers in the blood of patients with Huntington's disease. Neurol Res 34:721–724PubMed Sánchez-López F, Tasset I, Agüera E et al (2012) Oxidative stress and inflammation biomarkers in the blood of patients with Huntington's disease. Neurol Res 34:721–724PubMed
go back to reference Schöbitz B, de Kloet ER, Holsboer F (1994) Gene expression and function of interleukin 1, interleukin 6 and tumor necrosis factor in the brain. Prog Neurobiol 44:397–432PubMed Schöbitz B, de Kloet ER, Holsboer F (1994) Gene expression and function of interleukin 1, interleukin 6 and tumor necrosis factor in the brain. Prog Neurobiol 44:397–432PubMed
go back to reference Schöbitz B, de Kloet ER, Sutanto W, Holsboer F (1993) Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain. Eur J Neurosci 5:1426–1435PubMed Schöbitz B, de Kloet ER, Sutanto W, Holsboer F (1993) Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain. Eur J Neurosci 5:1426–1435PubMed
go back to reference Shalit F, Sredni B, Stern L et al (1994) Elevated interleukin-6 secretion levels by mononuclear cells of Alzheimer's patients. Neurosci Lett 174:130–132PubMed Shalit F, Sredni B, Stern L et al (1994) Elevated interleukin-6 secretion levels by mononuclear cells of Alzheimer's patients. Neurosci Lett 174:130–132PubMed
go back to reference Shapiro LS, Farrell J, Haghighi AB (2012) Tocilizumab treatment for neuro-Behcet's disease, the first report. Clin Neurol Neurosurg 114:297–298PubMed Shapiro LS, Farrell J, Haghighi AB (2012) Tocilizumab treatment for neuro-Behcet's disease, the first report. Clin Neurol Neurosurg 114:297–298PubMed
go back to reference Shaw PJ, Bates D, Cartlidge NE et al (1987) Long-term intellectual dysfunction following coronary artery bypass graft surgery: a six month follow-up study. Q J Med 62:259–268PubMed Shaw PJ, Bates D, Cartlidge NE et al (1987) Long-term intellectual dysfunction following coronary artery bypass graft surgery: a six month follow-up study. Q J Med 62:259–268PubMed
go back to reference Shibata N, Ohnuma T, Takahashi T et al (2002) Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype-phenotype association study in Japanese cases. Am J Med Genet 114:436–439PubMed Shibata N, Ohnuma T, Takahashi T et al (2002) Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype-phenotype association study in Japanese cases. Am J Med Genet 114:436–439PubMed
go back to reference Shrikant P, Weber E, Jilling T, Benveniste EN (1995) Intercellular adhesion molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6. J Immunol 155:1489–1501PubMed Shrikant P, Weber E, Jilling T, Benveniste EN (1995) Intercellular adhesion molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6. J Immunol 155:1489–1501PubMed
go back to reference Silvestroni A, Faull RLM, Strand AD, Möller T (2009) Distinct neuroinflammatory profile in post-mortem human Huntington's disease. Neuroreport 20:1098–1103PubMed Silvestroni A, Faull RLM, Strand AD, Möller T (2009) Distinct neuroinflammatory profile in post-mortem human Huntington's disease. Neuroreport 20:1098–1103PubMed
go back to reference Singh VK, Guthikonda P (1997) Circulating cytokines in Alzheimer's disease. J Psychiatr Res 31:657–660PubMed Singh VK, Guthikonda P (1997) Circulating cytokines in Alzheimer's disease. J Psychiatr Res 31:657–660PubMed
go back to reference Spronk PE, ter Borg EJ, Limburg PC, Kallenberg CG (1992) Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity? Clin Exp Immunol 90:106–110PubMedPubMedCentral Spronk PE, ter Borg EJ, Limburg PC, Kallenberg CG (1992) Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity? Clin Exp Immunol 90:106–110PubMedPubMedCentral
go back to reference Steffensen SC, Campbell IL, Henriksen SJ (1994) Site-specific hippocampal pathophysiology due to cerebral overexpression of interleukin-6 in transgenic mice. Brain Res 652:149–153PubMed Steffensen SC, Campbell IL, Henriksen SJ (1994) Site-specific hippocampal pathophysiology due to cerebral overexpression of interleukin-6 in transgenic mice. Brain Res 652:149–153PubMed
go back to reference Stojanovic A, Martorell L, Montalvo I et al (2014) Increased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology 41:23–32PubMed Stojanovic A, Martorell L, Montalvo I et al (2014) Increased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology 41:23–32PubMed
go back to reference Strauss S, Bauer J, Ganter U et al (1992) Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients. Lab Invest 66:223–230PubMed Strauss S, Bauer J, Ganter U et al (1992) Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients. Lab Invest 66:223–230PubMed
go back to reference Stys PK, Jiang Q (2002) Calpain-dependent neurofilament breakdown in anoxic and ischemic rat central axons. Neurosci Lett 328:150–154PubMed Stys PK, Jiang Q (2002) Calpain-dependent neurofilament breakdown in anoxic and ischemic rat central axons. Neurosci Lett 328:150–154PubMed
go back to reference Suzuki S, Tanaka K, Nagata E et al (1999) Cerebral neurons express interleukin-6 after transient forebrain ischemia in gerbils. Neurosci Lett 262:117–120PubMed Suzuki S, Tanaka K, Nagata E et al (1999) Cerebral neurons express interleukin-6 after transient forebrain ischemia in gerbils. Neurosci Lett 262:117–120PubMed
go back to reference Tancredi V, D'Antuono M, Cafè C et al (2000) The inhibitory effects of interleukin-6 on synaptic plasticity in the rat hippocampus are associated with an inhibition of mitogen-activated protein kinase ERK. J Neurochem 75:634–643PubMed Tancredi V, D'Antuono M, Cafè C et al (2000) The inhibitory effects of interleukin-6 on synaptic plasticity in the rat hippocampus are associated with an inhibition of mitogen-activated protein kinase ERK. J Neurochem 75:634–643PubMed
go back to reference Tarkowski E, Blennow K, Wallin A, Tarkowski A (1999) Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia. J Clin Immunol 19:223–230PubMed Tarkowski E, Blennow K, Wallin A, Tarkowski A (1999) Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia. J Clin Immunol 19:223–230PubMed
go back to reference Tarkowski E, Liljeroth AM, Minthon L et al (2003) Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull 61:255–260PubMed Tarkowski E, Liljeroth AM, Minthon L et al (2003) Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull 61:255–260PubMed
go back to reference Tatemichi TK, Desmond DW, Stern Y et al (1994) Cognitive impairment after stroke: frequency, patterns, and relationship to functional abilities. J Neurol Neurosurg Psychiatr 57:202–207PubMedPubMedCentral Tatemichi TK, Desmond DW, Stern Y et al (1994) Cognitive impairment after stroke: frequency, patterns, and relationship to functional abilities. J Neurol Neurosurg Psychiatr 57:202–207PubMedPubMedCentral
go back to reference Toulmond S, Vige X, Fage D, Benavides J (1992) Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons. Neurosci Lett 144:49–52PubMed Toulmond S, Vige X, Fage D, Benavides J (1992) Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons. Neurosci Lett 144:49–52PubMed
go back to reference Trysberg E, Carlsten H, Tarkowski A (2000) Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus 9:498–503PubMed Trysberg E, Carlsten H, Tarkowski A (2000) Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus 9:498–503PubMed
go back to reference Urbaniak P, Hasler P, Kretzschmar S (2012) Refractory neuro-Behçet treated by tocilizumab: a case report. Clin Exp Rheumatol 30:S73–5PubMed Urbaniak P, Hasler P, Kretzschmar S (2012) Refractory neuro-Behçet treated by tocilizumab: a case report. Clin Exp Rheumatol 30:S73–5PubMed
go back to reference Vallières L, Campbell IL, Gage FH, Sawchenko PE (2002) Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 22:486–492PubMed Vallières L, Campbell IL, Gage FH, Sawchenko PE (2002) Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 22:486–492PubMed
go back to reference Vallières L, Rivest S (1997) Regulation of the genes encoding interleukin-6, its receptor, and gp130 in the rat brain in response to the immune activator lipopolysaccharide and the proinflammatory cytokine interleukin-1beta. J Neurochem 69:1668–1683PubMed Vallières L, Rivest S (1997) Regulation of the genes encoding interleukin-6, its receptor, and gp130 in the rat brain in response to the immune activator lipopolysaccharide and the proinflammatory cytokine interleukin-1beta. J Neurochem 69:1668–1683PubMed
go back to reference van Duijn CM, Hofman A, Nagelkerken L (1990) Serum levels of interleukin-6 are not elevated in patients with Alzheimer's disease. Neurosci Lett 108:350–354PubMed van Duijn CM, Hofman A, Nagelkerken L (1990) Serum levels of interleukin-6 are not elevated in patients with Alzheimer's disease. Neurosci Lett 108:350–354PubMed
go back to reference Varghese JN, Moritz RL, Lou M-Z et al (2002) Structure of the extracellular domains of the human interleukin-6 receptor alpha -chain. Proc Natl Acad Sci USA 99:15959–15964PubMedPubMedCentral Varghese JN, Moritz RL, Lou M-Z et al (2002) Structure of the extracellular domains of the human interleukin-6 receptor alpha -chain. Proc Natl Acad Sci USA 99:15959–15964PubMedPubMedCentral
go back to reference Visser M, Pahor M, Taaffe DR et al (2002) Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57:M326–32PubMed Visser M, Pahor M, Taaffe DR et al (2002) Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci 57:M326–32PubMed
go back to reference Wada-Isoe K, Wakutani Y, Urakami K, Nakashima K (2004) Elevated interleukin-6 levels in cerebrospinal fluid of vascular dementia patients. Acta Neurol Scand 110:124–127PubMed Wada-Isoe K, Wakutani Y, Urakami K, Nakashima K (2004) Elevated interleukin-6 levels in cerebrospinal fluid of vascular dementia patients. Acta Neurol Scand 110:124–127PubMed
go back to reference Wallenius K, Wallenius V, Sunter D et al (2002) Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun 293:560–565PubMed Wallenius K, Wallenius V, Sunter D et al (2002) Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun 293:560–565PubMed
go back to reference Wang J, Dunn AJ (1998) Mouse interleukin-6 stimulates the HPA axis and increases brain tryptophan and serotonin metabolism. Neurochemistry International 33:143–154PubMed Wang J, Dunn AJ (1998) Mouse interleukin-6 stimulates the HPA axis and increases brain tryptophan and serotonin metabolism. Neurochemistry International 33:143–154PubMed
go back to reference Waterloo K, Omdal R, Husby G, Mellgren SI (2002) Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study. Rheumatology (Oxford) 41:411–415 Waterloo K, Omdal R, Husby G, Mellgren SI (2002) Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study. Rheumatology (Oxford) 41:411–415
go back to reference Weaver JD, Huang M-H, Albert M et al (2002) Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 59:371–378PubMed Weaver JD, Huang M-H, Albert M et al (2002) Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 59:371–378PubMed
go back to reference Wei H, Alberts I, Li X (2013) Brain IL-6 and autism. Neuroscience 252:320–325PubMed Wei H, Alberts I, Li X (2013) Brain IL-6 and autism. Neuroscience 252:320–325PubMed
go back to reference Wood JA, Wood PL, Ryan R et al (1993) Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1 beta or IL-1RA but increases in the associated acute phase proteins IL-6, alpha 2-macroglobulin and C-reactive protein. Brain Res 629:245–252PubMed Wood JA, Wood PL, Ryan R et al (1993) Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1 beta or IL-1RA but increases in the associated acute phase proteins IL-6, alpha 2-macroglobulin and C-reactive protein. Brain Res 629:245–252PubMed
go back to reference Wu Y, Shaghaghi EK, Jacquot C et al (1999) Synergism between interleukin-6 and interleukin-1beta in hypothalamic serotonin release: a reverse in vivo microdialysis study in F344 rats. Eur Cytokine Netw 10:57–64PubMed Wu Y, Shaghaghi EK, Jacquot C et al (1999) Synergism between interleukin-6 and interleukin-1beta in hypothalamic serotonin release: a reverse in vivo microdialysis study in F344 rats. Eur Cytokine Netw 10:57–64PubMed
go back to reference Xiao E, Xia L, Ferin M, Wardlaw SL (1999) Intracerebroventricular injection of interleukin-1 stimulates the release of high levels of interleukin-6 and interleukin-1 receptor antagonist into peripheral blood in the primate. Journal of Neuroimmunology 97:70–76PubMed Xiao E, Xia L, Ferin M, Wardlaw SL (1999) Intracerebroventricular injection of interleukin-1 stimulates the release of high levels of interleukin-6 and interleukin-1 receptor antagonist into peripheral blood in the primate. Journal of Neuroimmunology 97:70–76PubMed
go back to reference Yaffe K, Kanaya A, Lindquist K et al (2004) The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 292:2237–2242PubMed Yaffe K, Kanaya A, Lindquist K et al (2004) The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 292:2237–2242PubMed
go back to reference Yamada M, Hatanaka H (1994) Interleukin-6 protects cultured rat hippocampal neurons against glutamate-induced cell death. Brain Res 643:173–180PubMed Yamada M, Hatanaka H (1994) Interleukin-6 protects cultured rat hippocampal neurons against glutamate-induced cell death. Brain Res 643:173–180PubMed
go back to reference Yamakawa Y, Sugita Y, Nagatani T et al (1996) Interleukin-6 (IL-6) in patients with Behçet's disease. J Dermatol Sci 11:189–195PubMed Yamakawa Y, Sugita Y, Nagatani T et al (1996) Interleukin-6 (IL-6) in patients with Behçet's disease. J Dermatol Sci 11:189–195PubMed
go back to reference Zalcman S, Green-Johnson JM, Murray L et al (1994) Cytokine-specific central monoamine alterations induced by interleukin-1, −2 and −6. Brain Res 643:40–49PubMed Zalcman S, Green-Johnson JM, Murray L et al (1994) Cytokine-specific central monoamine alterations induced by interleukin-1, −2 and −6. Brain Res 643:40–49PubMed
go back to reference Zhang J, Terreni L, De Simoni MG, Dunn AJ (2001) Peripheral interleukin-6 administration increases extracellular concentrations of serotonin and the evoked release of serotonin in the rat striatum. Neurochemistry International 38:303–308PubMed Zhang J, Terreni L, De Simoni MG, Dunn AJ (2001) Peripheral interleukin-6 administration increases extracellular concentrations of serotonin and the evoked release of serotonin in the rat striatum. Neurochemistry International 38:303–308PubMed
go back to reference Zhao S-J, Guo C-N, Wang M-Q et al (2012) Serum levels of inflammation factors and cognitive performance in amnestic mild cognitive impairment: a Chinese clinical study. Cytokine 57:221–225PubMed Zhao S-J, Guo C-N, Wang M-Q et al (2012) Serum levels of inflammation factors and cognitive performance in amnestic mild cognitive impairment: a Chinese clinical study. Cytokine 57:221–225PubMed
go back to reference Zhong J, Dietzel ID, Wahle P et al (1999) Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice. J Neurosci 19:4305–4313PubMed Zhong J, Dietzel ID, Wahle P et al (1999) Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice. J Neurosci 19:4305–4313PubMed
go back to reference Zuliani G, Guerra G, Ranzini M et al (2007a) High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia. Int J Geriatr Psychiatry 22:305–311PubMed Zuliani G, Guerra G, Ranzini M et al (2007a) High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia. Int J Geriatr Psychiatry 22:305–311PubMed
go back to reference Zuliani G, Ranzini M, Guerra G, et al. (2007b) Plasma cytokines profile in older subjects with late onset Alzheimer’s disease or vascular dementia. J Psychiatr Res 41:686–693 Zuliani G, Ranzini M, Guerra G, et al. (2007b) Plasma cytokines profile in older subjects with late onset Alzheimer’s disease or vascular dementia. J Psychiatr Res 41:686–693
Metadata
Title
Interleukin 6 and cognitive dysfunction
Authors
Isabel Trapero
Omar Cauli
Publication date
01-09-2014
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 3/2014
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-014-9551-2

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