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Published in: Journal of NeuroVirology 2/2013

01-04-2013

Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China

Authors: Lin Yuan, Luxin Qiao, Feili Wei, Jiming Yin, Lifeng Liu, Yunxia Ji, Davey Smith, Ning Li, Dexi Chen

Published in: Journal of NeuroVirology | Issue 2/2013

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Abstract

In the current era of highly active antiretroviral therapy (HAART), the incidence of HIV dementia has declined, but the prevalence of HIV-associated neurocognitive disorder (HAND) remains high. HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND. Changes in cytokine levels in the cerebrospinal fluid (CSF) during HIV infection might help to identify HAND. To investigate whether the cytokine profile of the CSF during HIV infection could be used as a biomarker of HAND, we compared cytokine levels in the CSF of HIV-infected cases with and without neurocognitive impairment. Cytokine concentrations in the CSF were measured by quantification bioassays (Luminex xMAP). HIV-infected cases with neurocognitive impairment demonstrated higher levels of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, induced protein (IP)-10, and granulocyte colony-stimulating factor (G-CSF) in the CSF than those without neurocognitive impairment (G-CSF (p = 0.0003), IL-8 (p = 0.0046), IP-10 (p < 0.0001), and MCP-1 (p < 0.0001)). There was no significant impact of HAART on cytokine levels in the CSF, except for IP-10, which was higher in HAART-treated patients with impaired cognition (p = 0.0182). Findings from this preliminary study suggest that elevated levels of the cytokines IL-8, MCP-1, G-CSF, and IP-10 in the CSF are associated with neurocognitive impairment in HIV infection, and these cytokines likely represent a biomarker profile for HAND.
Literature
go back to reference Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–99PubMedCrossRef Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–99PubMedCrossRef
go back to reference Aquaro S, Ronga L, Pollicita M, Antinori A, Ranazzi A, Perno CF (2005) Human immunedeficiency virus infection and acquired immunodeficiency syndrome dementia complex: role of cells of monocyte-macrophage lineage. J Neurovirol 11:58–66. doi:10.1080/13550280500513416 PubMedCrossRef Aquaro S, Ronga L, Pollicita M, Antinori A, Ranazzi A, Perno CF (2005) Human immunedeficiency virus infection and acquired immunodeficiency syndrome dementia complex: role of cells of monocyte-macrophage lineage. J Neurovirol 11:58–66. doi:10.​1080/​1355028050051341​6 PubMedCrossRef
go back to reference Bandaru VV, McArthur JC, Sacktor N, Cutler RG, Knapp EL, Mattson MP et al (2007) Associative and predictive biomarkers of dementia in HIV-1-infected patients. Neurology 68:1481–7PubMedCrossRef Bandaru VV, McArthur JC, Sacktor N, Cutler RG, Knapp EL, Mattson MP et al (2007) Associative and predictive biomarkers of dementia in HIV-1-infected patients. Neurology 68:1481–7PubMedCrossRef
go back to reference Bebell LM, Passmore JA, Williamson C, Mlisana K, Iriogbe I, Loggerenberg F et al (2008) Relationship between levels of inflammatory cytokines in the genital tract and CD4+ cell counts in women with acute HIV-1 infection. J Infect Dis 198:710–4. doi:10.1086/590503 PubMedCrossRef Bebell LM, Passmore JA, Williamson C, Mlisana K, Iriogbe I, Loggerenberg F et al (2008) Relationship between levels of inflammatory cytokines in the genital tract and CD4+ cell counts in women with acute HIV-1 infection. J Infect Dis 198:710–4. doi:10.​1086/​590503 PubMedCrossRef
go back to reference Clifford DB, Fagan AM, Holtzman DM, Morris JC, Teshome M, Shah AR et al (2009) CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology 73:1982–7PubMedCrossRef Clifford DB, Fagan AM, Holtzman DM, Morris JC, Teshome M, Shah AR et al (2009) CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology 73:1982–7PubMedCrossRef
go back to reference Epstein LG, Gendelman HE (1993) Human immunodeficiency virus type-1 infection of the nervous system: pathogenetic mechanisms. Ann Neurol 33:429–36PubMedCrossRef Epstein LG, Gendelman HE (1993) Human immunodeficiency virus type-1 infection of the nervous system: pathogenetic mechanisms. Ann Neurol 33:429–36PubMedCrossRef
go back to reference Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW (2006) CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood–brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. J Neurosci 26:1098–106. doi:10.1523/JNEUROSCI.3863-05.2006 PubMedCrossRef Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW (2006) CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood–brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS. J Neurosci 26:1098–106. doi:10.​1523/​JNEUROSCI.​3863-05.​2006 PubMedCrossRef
go back to reference Gonzalez E, Rovin BH, Sen L, Cooke G, Dhanda R, Mummidi S (2002) HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proc Natl Acad Sci U S A 99:13795–800PubMedCrossRef Gonzalez E, Rovin BH, Sen L, Cooke G, Dhanda R, Mummidi S (2002) HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proc Natl Acad Sci U S A 99:13795–800PubMedCrossRef
go back to reference Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F et al (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087–96PubMedCrossRef Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F et al (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087–96PubMedCrossRef
go back to reference Hopkins SJ (1995) Cytokines and the nervous system. I: Expression and recognition. Trends Neurosci 18:83–8PubMedCrossRef Hopkins SJ (1995) Cytokines and the nervous system. I: Expression and recognition. Trends Neurosci 18:83–8PubMedCrossRef
go back to reference Lehmann MH, Masanetz S, Kramer S, Erfle V (2006) HIV-1 Nef upregulates CCL2/MCP-1 expression in astrocytes in a myristoylation- and calmodulin-dependent manner. J Cell Sci 119:4520–30. doi:10.1242/jcs.03231 PubMedCrossRef Lehmann MH, Masanetz S, Kramer S, Erfle V (2006) HIV-1 Nef upregulates CCL2/MCP-1 expression in astrocytes in a myristoylation- and calmodulin-dependent manner. J Cell Sci 119:4520–30. doi:10.​1242/​jcs.​03231 PubMedCrossRef
go back to reference Letendre SL, Zheng JC, Kaul M, Yiannoutsos CT, Ellis RJ, Taylor MJ et al (2011) Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals. J Neurovirol 17:63–9. doi:10.1007/s13365-010-0013-2 PubMedCrossRef Letendre SL, Zheng JC, Kaul M, Yiannoutsos CT, Ellis RJ, Taylor MJ et al (2011) Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals. J Neurovirol 17:63–9. doi:10.​1007/​s13365-010-0013-2 PubMedCrossRef
go back to reference Persidsky Y, Zheng J, Miller D, Gendelman HE (2000) Mononuclear phagocytes mediate blood–brain barrier compromise and neuronal injury during HIV-1-associated dementia. J Leukoc Biol 68:413–22PubMed Persidsky Y, Zheng J, Miller D, Gendelman HE (2000) Mononuclear phagocytes mediate blood–brain barrier compromise and neuronal injury during HIV-1-associated dementia. J Leukoc Biol 68:413–22PubMed
go back to reference Price RW, Epstein LG, Becker JT, Cinque P, Gisslen M, Pulliam L et al (2007) Biomarkers of HIV-1 CNS infection and injury. Neurology 69:1781–8PubMedCrossRef Price RW, Epstein LG, Becker JT, Cinque P, Gisslen M, Pulliam L et al (2007) Biomarkers of HIV-1 CNS infection and injury. Neurology 69:1781–8PubMedCrossRef
go back to reference Shah A, Kumar A (2010) HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated through the NF-κB pathway and can be silenced by gp120-specific siRNA. J Neuroinflammation 7:96–101PubMedCrossRef Shah A, Kumar A (2010) HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated through the NF-κB pathway and can be silenced by gp120-specific siRNA. J Neuroinflammation 7:96–101PubMedCrossRef
Metadata
Title
Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China
Authors
Lin Yuan
Luxin Qiao
Feili Wei
Jiming Yin
Lifeng Liu
Yunxia Ji
Davey Smith
Ning Li
Dexi Chen
Publication date
01-04-2013
Publisher
Springer US
Published in
Journal of NeuroVirology / Issue 2/2013
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-013-0150-5

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