Skip to main content
Top
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Subarachnoid Hemorrhage | Research

The role of cortisol in immunosuppression in subarachnoid haemorrhage

Authors: Margaret E. Hoadley, James Galea, Navneet Singh, Sharon Hulme, David O. Ajao, Nancy Rothwell, Andrew King, Pippa Tyrrell, Stephen J. Hopkins

Published in: European Journal of Medical Research | Issue 1/2023

Login to get access

Abstract

Background

We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH).

Methods

Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity.

Results

Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses.

Conclusion

These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.
Literature
1.
go back to reference Bartanusz V, Corneille MG, Sorda S, Gildea M, Michalek J, Nair PV, Stewart RM, Jezova D. Diurnal salivary cortisol measurement in the neurosurgical-surgical intensive care unit in critically ill acute trauma patients. J Clin Neurosci. 2014;12:2150–4. Bartanusz V, Corneille MG, Sorda S, Gildea M, Michalek J, Nair PV, Stewart RM, Jezova D. Diurnal salivary cortisol measurement in the neurosurgical-surgical intensive care unit in critically ill acute trauma patients. J Clin Neurosci. 2014;12:2150–4.
2.
go back to reference Benarroch EE. Autonomic-mediated immunomodulation and potential clinical relevance. Neurology. 2009;73:236–42.PubMed Benarroch EE. Autonomic-mediated immunomodulation and potential clinical relevance. Neurology. 2009;73:236–42.PubMed
3.
go back to reference Bertagna X, Bertagna C, Luton JP, Husson JM, Girard F. The new steroid analog RU 486 inhibits glucocorticoid action in man. J Clin Endocrinol Metab. 1984;59:25–8.PubMed Bertagna X, Bertagna C, Luton JP, Husson JM, Girard F. The new steroid analog RU 486 inhibits glucocorticoid action in man. J Clin Endocrinol Metab. 1984;59:25–8.PubMed
4.
go back to reference Breuninger LM, Dempsey WL, Uhl J, Murasko DM. Hydrocortisone regulation of interleukin-6 protein production by a purified population of human peripheral blood monocytes. Clin Immunol Immunopathol. 1993;69:205–14.PubMed Breuninger LM, Dempsey WL, Uhl J, Murasko DM. Hydrocortisone regulation of interleukin-6 protein production by a purified population of human peripheral blood monocytes. Clin Immunol Immunopathol. 1993;69:205–14.PubMed
5.
6.
go back to reference Chamorro A, Urra X, Planas AM. Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke. 2007;38:1097–103.PubMed Chamorro A, Urra X, Planas AM. Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression. Stroke. 2007;38:1097–103.PubMed
7.
go back to reference Chang CP, Wang SW, Huang ZL, Wang OY, Huang MI, Lu LM, Tarng DC, Chien CH, Chien EJ. Non-genomic rapid inhibition of Na+/H+-exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids. J Cell Physiol. 2010;223:679–86.PubMed Chang CP, Wang SW, Huang ZL, Wang OY, Huang MI, Lu LM, Tarng DC, Chien CH, Chien EJ. Non-genomic rapid inhibition of Na+/H+-exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids. J Cell Physiol. 2010;223:679–86.PubMed
8.
go back to reference Check JH, Wikson C, Cohen R, Sarumi M. Evidence that mifepristone, a progesterone receptor antagonist, can cross the blood brain barrier and provide palliative benefits for glioblastoma multiforme grade IV. Anticancer Res. 2014;34:2385–8.PubMed Check JH, Wikson C, Cohen R, Sarumi M. Evidence that mifepristone, a progesterone receptor antagonist, can cross the blood brain barrier and provide palliative benefits for glioblastoma multiforme grade IV. Anticancer Res. 2014;34:2385–8.PubMed
9.
go back to reference Czlonkowska A, Cyrta B, Korlak J. Immunological observations on patients with acute cerebral vascular disease. J Neurol Sci. 1979;43:455–64.PubMed Czlonkowska A, Cyrta B, Korlak J. Immunological observations on patients with acute cerebral vascular disease. J Neurol Sci. 1979;43:455–64.PubMed
10.
go back to reference Damsgaard CT, Lauritzen L, Calder PC, Kjaer TM, Frokiaer H. Whole-blood culture is a valid low-cost method to measure monocytic cytokines—a comparison of cytokine production in cultures of human whole-blood, mononuclear cells and monocytes. J Immunol Methods. 2009;340:95–101.PubMed Damsgaard CT, Lauritzen L, Calder PC, Kjaer TM, Frokiaer H. Whole-blood culture is a valid low-cost method to measure monocytic cytokines—a comparison of cytokine production in cultures of human whole-blood, mononuclear cells and monocytes. J Immunol Methods. 2009;340:95–101.PubMed
11.
go back to reference DeRijk R, Michelson D, Karp B, Petrides J, Galliven E, Deuster P, Paciotti G, Gold PW, Sternberg EM. Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) production in humans: high sensitivity of TNF alpha and resistance of IL-6. J Clin Endocrinol Metab. 1997;82:2182–91.PubMed DeRijk R, Michelson D, Karp B, Petrides J, Galliven E, Deuster P, Paciotti G, Gold PW, Sternberg EM. Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) production in humans: high sensitivity of TNF alpha and resistance of IL-6. J Clin Endocrinol Metab. 1997;82:2182–91.PubMed
12.
go back to reference Dirnagl U, Khlemet J, Braun JS, Harms H, Meisel C, Ziemssen T, Prass K, Meisel A. Stroke-induced immunodepression: experimental evidence and clinical relevance. Stroke. 2007;38:770–73.PubMed Dirnagl U, Khlemet J, Braun JS, Harms H, Meisel C, Ziemssen T, Prass K, Meisel A. Stroke-induced immunodepression: experimental evidence and clinical relevance. Stroke. 2007;38:770–73.PubMed
13.
go back to reference Edwards, et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury—outcomes at 6 months. The Lancet. 2005;365:1957–9. Edwards, et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury—outcomes at 6 months. The Lancet. 2005;365:1957–9.
14.
go back to reference Emsley HC, Hopkins SJ. Acute ischaemic stroke and infection: recent and emerging concepts. Lancet Neurol. 2008;7:341–53.PubMed Emsley HC, Hopkins SJ. Acute ischaemic stroke and infection: recent and emerging concepts. Lancet Neurol. 2008;7:341–53.PubMed
15.
go back to reference Emsley HC, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Hallenbeck JM, del Zoppo GJ, Rothwell NJ, Tyrrell PJ, Hopkins SJ. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J Neuroimmunol. 2003;139:93–101.PubMed Emsley HC, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Hallenbeck JM, del Zoppo GJ, Rothwell NJ, Tyrrell PJ, Hopkins SJ. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J Neuroimmunol. 2003;139:93–101.PubMed
16.
go back to reference Emsley HC, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Illingworth K, Scarth S, Wickramasinghe V, Hoadley ME, Rothwell NJ, Tyrrell PJ, Hopkins SJ. Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production. BMC Neurol. 2007;7:5.PubMedPubMedCentral Emsley HC, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Illingworth K, Scarth S, Wickramasinghe V, Hoadley ME, Rothwell NJ, Tyrrell PJ, Hopkins SJ. Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production. BMC Neurol. 2007;7:5.PubMedPubMedCentral
17.
go back to reference Franchimont D. Overview of the actions of glucocorticoids on the immune response: a good model to characterize new pathways of immunosuppression for new treatment strategies. Ann N Y Acad Sci. 2004;1024:124–37.PubMed Franchimont D. Overview of the actions of glucocorticoids on the immune response: a good model to characterize new pathways of immunosuppression for new treatment strategies. Ann N Y Acad Sci. 2004;1024:124–37.PubMed
18.
go back to reference Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, Parra A, Connolly ES, Mayer SA. Impact of nosocomial infectious complications after subarachnoid hemorrhage. Neurosurgery. 2008;62:80–7.PubMed Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, Parra A, Connolly ES, Mayer SA. Impact of nosocomial infectious complications after subarachnoid hemorrhage. Neurosurgery. 2008;62:80–7.PubMed
19.
20.
go back to reference Gonçalves B, Kurtzl P, Turon R, Santos T, Prazeres M, Righy C. Incidence and impact of sepsis on long-term outcomes after subarachnoid hemorrhage: a prospective observational study. Ann Intensive Care. 2019;9:94.PubMedPubMedCentral Gonçalves B, Kurtzl P, Turon R, Santos T, Prazeres M, Righy C. Incidence and impact of sepsis on long-term outcomes after subarachnoid hemorrhage: a prospective observational study. Ann Intensive Care. 2019;9:94.PubMedPubMedCentral
21.
go back to reference Helling TS, Evans LL, Fowler DL, Hays LV, Kennedy FR. Infectious complications in patients with severe head injury. J Trauma. 1988;28:1575–7.PubMed Helling TS, Evans LL, Fowler DL, Hays LV, Kennedy FR. Infectious complications in patients with severe head injury. J Trauma. 1988;28:1575–7.PubMed
22.
go back to reference Hong KS, Kang DW, Koo JS, Yu KH, Han MK, Cho YJ, Park JM, Bae HJ, Lee BC. Impact of neurological and medical complications on 3-month outcomes in acute ischaemic stroke. Eur J Neurol. 2008;15:1324–31.PubMed Hong KS, Kang DW, Koo JS, Yu KH, Han MK, Cho YJ, Park JM, Bae HJ, Lee BC. Impact of neurological and medical complications on 3-month outcomes in acute ischaemic stroke. Eur J Neurol. 2008;15:1324–31.PubMed
23.
go back to reference Hopkins S, McMahon C, Singh N, Galea J, Hoadley M, Scarth S, Patel H, Vail A, Hulme S, Rothwell N, King A, Tyrrell P. Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection. J Neuroinflamm. 2012;9:255. Hopkins S, McMahon C, Singh N, Galea J, Hoadley M, Scarth S, Patel H, Vail A, Hulme S, Rothwell N, King A, Tyrrell P. Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection. J Neuroinflamm. 2012;9:255.
24.
go back to reference Johnston KC, Li JY, Lyden PD, Hanson SK, Feasby TE, Adams RJ, Faught RE Jr, Haley EC Jr. Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators. Stroke. 1998;29:447–53.PubMed Johnston KC, Li JY, Lyden PD, Hanson SK, Feasby TE, Adams RJ, Faught RE Jr, Haley EC Jr. Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators. Stroke. 1998;29:447–53.PubMed
25.
go back to reference Kirchner H, Kleinicke C, Digel W. A whole-blood technique for testing production of human interferon by leukocytes. J Immunol Methods. 1982;48:213–9.PubMed Kirchner H, Kleinicke C, Digel W. A whole-blood technique for testing production of human interferon by leukocytes. J Immunol Methods. 1982;48:213–9.PubMed
26.
go back to reference Kourbeti IS, Vakis AF, Papadakis JA, Karabetsos DA, Bertsias G, Filippou M, Ioannou A, Neophytou C, Anastasaki M, Samonis G. Infections in traumatic brain injury patients. Clin Microbiol Infect. 2012;18:359–64.PubMed Kourbeti IS, Vakis AF, Papadakis JA, Karabetsos DA, Bertsias G, Filippou M, Ioannou A, Neophytou C, Anastasaki M, Samonis G. Infections in traumatic brain injury patients. Clin Microbiol Infect. 2012;18:359–64.PubMed
27.
go back to reference Larsen MH, Albrechtsen A, Thorner LW, Werge T, Hansen T, Gether U, Haastrup E, Ullum H. Genome-wide association study of genetic variants in LPS-stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-alpha cytokine response in a Danish cohort. PLoS ONE. 2013;8:e66262.PubMedPubMedCentral Larsen MH, Albrechtsen A, Thorner LW, Werge T, Hansen T, Gether U, Haastrup E, Ullum H. Genome-wide association study of genetic variants in LPS-stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-alpha cytokine response in a Danish cohort. PLoS ONE. 2013;8:e66262.PubMedPubMedCentral
28.
go back to reference Linden M, Brattsand R. Effects of a corticosteroid, budesonide, on alveolar macrophage and blood monocyte secretion of cytokines: differential sensitivity of GM-CSF, IL-1 beta, and IL-6. Pulm Pharmacol. 1994;7:43–7.PubMed Linden M, Brattsand R. Effects of a corticosteroid, budesonide, on alveolar macrophage and blood monocyte secretion of cytokines: differential sensitivity of GM-CSF, IL-1 beta, and IL-6. Pulm Pharmacol. 1994;7:43–7.PubMed
29.
go back to reference Lyte M. Generation and measurement of interleukin-1, interleukin-2, and mitogen levels in small volumes of whole blood. J Clin Lab Anal. 1987;1:83–8. Lyte M. Generation and measurement of interleukin-1, interleukin-2, and mitogen levels in small volumes of whole blood. J Clin Lab Anal. 1987;1:83–8.
30.
go back to reference Marklund N, Peltonen M, Nilsson TK, Olsson T. Low and high circulating cortisol levels predict mortality and cognitive dysfunction early after stroke. J Intern Med. 2004;256:15–21.PubMed Marklund N, Peltonen M, Nilsson TK, Olsson T. Low and high circulating cortisol levels predict mortality and cognitive dysfunction early after stroke. J Intern Med. 2004;256:15–21.PubMed
31.
go back to reference Meisel C, Volk HD. Mechanisms of immunodepression after central nervous system injury. In: Abraham E, Singer M, editors. Critical care medicine, vol. 35. Berlin: Springer; 2007. p. 2408–16. Meisel C, Volk HD. Mechanisms of immunodepression after central nervous system injury. In: Abraham E, Singer M, editors. Critical care medicine, vol. 35. Berlin: Springer; 2007. p. 2408–16.
32.
go back to reference Montgomerie JZ. Infections in patients with spinal cord injuries. Clin Infect Dis. 1997;25:1285–90 (quiz 1291-1282).PubMed Montgomerie JZ. Infections in patients with spinal cord injuries. Clin Infect Dis. 1997;25:1285–90 (quiz 1291-1282).PubMed
33.
go back to reference Olsson T, Marklund N, Gustafson Y, Nasman B. Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke. Stroke. 1992;23:1573–6.PubMed Olsson T, Marklund N, Gustafson Y, Nasman B. Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke. Stroke. 1992;23:1573–6.PubMed
35.
go back to reference Peeters BWMM, Tonnaer JADM, Groen MB, Broekkamp CLE, van der Voort HAA, Schoonen WGFJ, Smets RJM, Vanderheyden PML, Gebhard R, Ruigt GSF. Short Review Glucocorticoid receptor antagonists: new tools to investigate disorders characterized by cortisol hypersecretion. Stress. 2004;7:233–41.PubMed Peeters BWMM, Tonnaer JADM, Groen MB, Broekkamp CLE, van der Voort HAA, Schoonen WGFJ, Smets RJM, Vanderheyden PML, Gebhard R, Ruigt GSF. Short Review Glucocorticoid receptor antagonists: new tools to investigate disorders characterized by cortisol hypersecretion. Stress. 2004;7:233–41.PubMed
36.
go back to reference Sarrafzadeh A, Schlenk F, Meisel A, Dreier J, Vajkoczy P, Meisel C. Immunodepression after aneurysmal subarachnoid hemorrhage. Stroke. 2011;42:53–8.PubMed Sarrafzadeh A, Schlenk F, Meisel A, Dreier J, Vajkoczy P, Meisel C. Immunodepression after aneurysmal subarachnoid hemorrhage. Stroke. 2011;42:53–8.PubMed
37.
go back to reference Singh N, Hopkins S, Hulme S, Galea J, Hoadley M, Vail A, Hutchinson P, Grainger S, Rothwell N, King A, Tyrrell P. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial. J Neuroinflamm. 2014;11:1. Singh N, Hopkins S, Hulme S, Galea J, Hoadley M, Vail A, Hutchinson P, Grainger S, Rothwell N, King A, Tyrrell P. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial. J Neuroinflamm. 2014;11:1.
38.
go back to reference Smith CJ, Hedley E, Udeh CT, Vail A, Hoadley, ME, Rothwell NJ, Tyrrell P, Hopkins S. Interleukin-1 receptor antagonist reverses stroke-associated peripheral immune suppression. Cytokine. 2012;58;384–89. Smith CJ, Hedley E, Udeh CT, Vail A, Hoadley, ME, Rothwell NJ, Tyrrell P, Hopkins S. Interleukin-1 receptor antagonist reverses stroke-associated peripheral immune suppression. Cytokine. 2012;58;384–89.
39.
go back to reference Steer JH, Vuong Q, Joyce DA. Suppression of human monocyte tumour necrosis factor-alpha release by glucocorticoid therapy: relationship to systemic monocytopaenia and cortisol suppression. Br J Clin Pharmacol. 1997;43:383–9.PubMedPubMedCentral Steer JH, Vuong Q, Joyce DA. Suppression of human monocyte tumour necrosis factor-alpha release by glucocorticoid therapy: relationship to systemic monocytopaenia and cortisol suppression. Br J Clin Pharmacol. 1997;43:383–9.PubMedPubMedCentral
40.
go back to reference Sugarman B, Brown D, Musher D. Fever and infection in spinal cord injury patients. JAMA, J Am Med Assoc. 1982;248:66–70. Sugarman B, Brown D, Musher D. Fever and infection in spinal cord injury patients. JAMA, J Am Med Assoc. 1982;248:66–70.
41.
go back to reference Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994;83:113–8.PubMed Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994;83:113–8.PubMed
42.
go back to reference Uchakin PN, Smith SM, Uchakina ON. Hydrocortisone-modulated immune response and altered amino acid pool in vitro. J Endocrinol Metab. 2011;1:166–73. Uchakin PN, Smith SM, Uchakina ON. Hydrocortisone-modulated immune response and altered amino acid pool in vitro. J Endocrinol Metab. 2011;1:166–73.
43.
go back to reference van der Linden MW, Huizinga TW, Stoeken DJ, Sturk A, Westendorp RG. Determination of tumour necrosis factor-alpha and interleukin-10 production in a whole blood stimulation system: assessment of laboratory error and individual variation. J Immunol Methods. 1998;218:63–71.PubMed van der Linden MW, Huizinga TW, Stoeken DJ, Sturk A, Westendorp RG. Determination of tumour necrosis factor-alpha and interleukin-10 production in a whole blood stimulation system: assessment of laboratory error and individual variation. J Immunol Methods. 1998;218:63–71.PubMed
44.
go back to reference Van Voorhis BJ, Anderson DJ, Hill JA. The effects of RU 486 on immune function and steroid-induced immunosuppression in vitro. J Clin Endocrinol Metab. 1989;69:1195–9.PubMed Van Voorhis BJ, Anderson DJ, Hill JA. The effects of RU 486 on immune function and steroid-induced immunosuppression in vitro. J Clin Endocrinol Metab. 1989;69:1195–9.PubMed
45.
go back to reference Waage A, Bakke O. Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunology. 1988;63:299–302.PubMedPubMedCentral Waage A, Bakke O. Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunology. 1988;63:299–302.PubMedPubMedCentral
46.
go back to reference Westendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol. 2011;11:110.PubMedPubMedCentral Westendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol. 2011;11:110.PubMedPubMedCentral
47.
go back to reference Wirtz PH, von Kanel R, Kunz-Ebrecht S, Ehlert U, Fischer JE. Enhanced glucocorticoid sensitivity of cytokine release from circulating leukocytes stimulated with lipopolysaccharide in healthy male smokers. Brain Behav Immun. 2004;18:536–43.PubMed Wirtz PH, von Kanel R, Kunz-Ebrecht S, Ehlert U, Fischer JE. Enhanced glucocorticoid sensitivity of cytokine release from circulating leukocytes stimulated with lipopolysaccharide in healthy male smokers. Brain Behav Immun. 2004;18:536–43.PubMed
48.
go back to reference Wirtz PH, von Kanel R, Rohleder N, Fischer JE. Monocyte proinflammatory cytokine release is higher and glucocorticoid sensitivity is lower in middle aged men than in women independent of cardiovascular risk factors. Heart. 2004;90:853–8.PubMedPubMedCentral Wirtz PH, von Kanel R, Rohleder N, Fischer JE. Monocyte proinflammatory cytokine release is higher and glucocorticoid sensitivity is lower in middle aged men than in women independent of cardiovascular risk factors. Heart. 2004;90:853–8.PubMedPubMedCentral
49.
go back to reference Woiciechowsky C, Asadullah K, Nestler D, Eberhardt B, Platzer C, Schoning B, Glockner F, Lanksch WR, Volk HD, Docke WD. Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med. 1998;4:808–13.PubMed Woiciechowsky C, Asadullah K, Nestler D, Eberhardt B, Platzer C, Schoning B, Glockner F, Lanksch WR, Volk HD, Docke WD. Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med. 1998;4:808–13.PubMed
50.
go back to reference Woiciechowsky C, Schoning B, Cobanov J, Lanksch WR, Volk HD, Docke WD. Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain-injured patients. J Trauma. 2002;52:339–45.PubMed Woiciechowsky C, Schoning B, Cobanov J, Lanksch WR, Volk HD, Docke WD. Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain-injured patients. J Trauma. 2002;52:339–45.PubMed
51.
go back to reference Woiciechowsky C, Schoning B, Daberkow N, Asche K, Stoltenburg G, Lanksch WR, Volk HD. Brain-IL-1beta induces local inflammation but systemic anti-inflammatory response through stimulation of both hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Brain Res. 1999;816:563–71.PubMed Woiciechowsky C, Schoning B, Daberkow N, Asche K, Stoltenburg G, Lanksch WR, Volk HD. Brain-IL-1beta induces local inflammation but systemic anti-inflammatory response through stimulation of both hypothalamic-pituitary-adrenal axis and sympathetic nervous system. Brain Res. 1999;816:563–71.PubMed
52.
go back to reference Woiciechowsky C, Schoning B, Lanksch WR, Volk HD, Docke WD. Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. J Mol Med (Berl). 1999;77:769–80.PubMed Woiciechowsky C, Schoning B, Lanksch WR, Volk HD, Docke WD. Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. J Mol Med (Berl). 1999;77:769–80.PubMed
53.
go back to reference Wulsin AC, Herman JP, Danzer SC. RU486 mitigates hippocampal pathology following status epilepticus. Front Neurol. 2016;7:214.PubMedPubMedCentral Wulsin AC, Herman JP, Danzer SC. RU486 mitigates hippocampal pathology following status epilepticus. Front Neurol. 2016;7:214.PubMedPubMedCentral
54.
go back to reference Zetterling M, Engström B, Hallberg L, Hillered L, Enblad P, Karlsson T, Engström E. Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage. Br J Neurosurg. 2011;25:684.PubMed Zetterling M, Engström B, Hallberg L, Hillered L, Enblad P, Karlsson T, Engström E. Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage. Br J Neurosurg. 2011;25:684.PubMed
Metadata
Title
The role of cortisol in immunosuppression in subarachnoid haemorrhage
Authors
Margaret E. Hoadley
James Galea
Navneet Singh
Sharon Hulme
David O. Ajao
Nancy Rothwell
Andrew King
Pippa Tyrrell
Stephen J. Hopkins
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01222-3

Other articles of this Issue 1/2023

European Journal of Medical Research 1/2023 Go to the issue