Journal of Endocrinological Investigation

, Volume 27, Issue 1, pp 37–41 | Cite as

Serum interleukin-6 predicts cortisol release in acute stroke patients

  • A. Szczudlik
  • T. Dziedzic
  • S. Bartus
  • A. Slowik
  • A. Kieltyka
Original Article


Altered hypothalamo-pituitary-adrenal axis was reported in stroke patients; however, mechanisms responsible for this phenomenon are barely understood. Acute cerebral ischemia triggers interleukin-6 (IL-6) release into blood. Circulating IL-6 can stimulate hypothalamo-pituitary-adrenal axis. The goal of our study was to assess a relationship between serum IL-6 and cortisol in acute ischemic stroke. Twenty two patients with ischemic stroke and 17 controls were included. Serum samples were collected on the 2nd day of stroke at 6:00, 10:00 18:00, 22:00 h and at the same time points in control group. Cytokines and cortisol levels were measured using ELISA method. Serum IL-6 and cortisol levels were higher in stroke patients than in controls. Cortisol displayed diurnal variations in both stroke patients and controls. In contrast with control subjects, serum IL-6 levels did not display diurnal variations in stroke patients. In stroke patients, but not in controls, IL-6 level correlated significantly with cortisol level and morning serum IL-6 level independently predicted evening/night cortisol level. In conclusion, brain ischemia could stimulate IL-6 release in blood and in this way modulate hypothalamo-pituitary-adrenal axis.


Cortisol cytokines stroke cerebral ischemia 


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  1. 1.
    Olsson T. Urinary free cortisol excretion shortly after ischaemic stroke. J Intern Med 1990, 228: 177–81.PubMedCrossRefGoogle Scholar
  2. 2.
    Olsson T, Astrom M, Eriksson S, et al. Hypercortisolism revealed by the dexamethasone suppression test in patients with acute ischemic stroke. Stroke 1989, 20: 1685–90.PubMedCrossRefGoogle Scholar
  3. 3.
    Olsson T, Marklund N, Gustafson Y, et al. Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke. Stroke 1992, 23: 1573–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Murros K, Fogelholm R, Kettunen S, et al. Serum cortisol and outcome of ischemic brain infarction. J Neurol Sci 1993, 16: 12–7.CrossRefGoogle Scholar
  5. 5.
    Fassbender K, Schmidt R, Moessner R, et al. Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage and clinical outcome. Stroke 1994, 25: 1105–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Franceschini R, Gandolfo C, Cataldia A, et al. Twenty-four-hour β-endorphin secretory pattern in stroke patients. Stroke 1994, 25: 2142–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Slowik A, Turaj W, Pankiewicz J, et al. Hypercortisolemia in acute stroke is related to the inflammatory response. J Neurol Sci 2002, 196: 27–32.PubMedCrossRefGoogle Scholar
  8. 8.
    Turnbull AV, Rivier C. Regulation of the HPA axis by cytokines. Brain Behav Immun 1995, 9: 253–75.PubMedCrossRefGoogle Scholar
  9. 9.
    Gaillard RC. Interaction between the hypothalamo-pituitary-adrenal axis and the immunological system. Ann Endocrinol (Paris) 2001, 62: 155–63.Google Scholar
  10. 10.
    Brott T, Marler JR, Olinger CP, et al. Measurements of acute cerebral infarction: lesion size by computed tompgraphy. Stroke 1989, 20: 871–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Adams HP, Bendixen BH, Kappelle LJ, and the TOAST investigators. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. Stroke 1993, 24: 35–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Gustafson Y, Olsson T, Asplund K, et al. Acute confusional states early after stroke is associated with hypercortisolism. Cerebrovasc Dis 1993, 3: 33–8.CrossRefGoogle Scholar
  13. 13.
    Astrom M, Olsson T, Asplund K. Different linkage of major depression to hypercortisolism early versus late after stroke: results from a 3-year longitudinal study. Stroke 1993, 24: 52–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Oka M. Effect of cerebrovascular accident on the level of 17-hydroxycorticosteroids in plasma. Acta Med Scand 1956, 154: 221–6.Google Scholar
  15. 15.
    O’Neill PA, Davies I, Fullerton KJ, et al. Stress hormone and blood glucose response following acute stroke in the elderly. Stroke 1991, 22: 842–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Haack M, Reichenberg A, Kraus T, et al. Effects of an intravenous catheter on the local production of cytokines and soluble cytokine receptors in healthy men. Cytokine 2000, 12: 694–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999, 100: 793–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Tarkowski E, Rosengren L, Blomstrand C, et al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke 1995, 26: 1393–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Fassbender K, Rossol S, Kammer T, et al. Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease. J Neurol Sci 1994, 122: 135–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Beamer NB, Coull BM, Clark WM, et al. Interleukin-6 and interleukin-1 receptor antagonist in acute stroke. Ann Neurol 1995, 37: 800–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Kim JS, Yoon SS, Kim YH, et al. Serial measurement of interleukin-6, transforming growth factor-β, and S-100 protein in patients with acute stroke. Stroke 1996, 27: 1553–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Ferrarese C, Mascarucci P, Zoia C, et al. Increased cytokine release from peripheral blood cells after acute stroke. J Cereb Blood Flow Metab 1999, 19: 1004–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Perini VF, Morra M, Alecci M, et al. Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients. Neurol Sci 2001, 22: 289–96.PubMedCrossRefGoogle Scholar
  24. 24.
    Sothern RB, Roitman-Johnson B, Kanabrocki EL et al. Circadian characteristics of circulating interleukin-6 in men. J Allergy Clin Immunol 1995, 95: 1029–35.PubMedCrossRefGoogle Scholar
  25. 25.
    Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab 1993, 77: 1690–4.PubMedGoogle Scholar
  26. 26.
    Spath-Schwalbe E, Born J, Schrezenmeier H, et al. Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man. J Clin Endocrinol Metab 1994, 79: 1212–4.PubMedGoogle Scholar
  27. 27.
    Judd AM, Call GB, Barney M, et al. Possible function of IL-6 and TNF as intraadrenal factors in the regulation of adrenal steroid secretion. Ann NY Acad Sci 2000, 917: 628–37.PubMedCrossRefGoogle Scholar
  28. 28.
    Johansson A, Olsson T, Carlberg B, et al. Hypercortisolism after stroke — partly cytokine mediated? J Neurol Sci 1997, 147: 43–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Johansson A, Ahren B, Nasman B, et al. Cortisol axis abnormalities early after stroke — relationship to cytokines and leptin. J Inter Med 2000, 247: 179–87.CrossRefGoogle Scholar
  30. 30.
    De Rijk R, Michelson D, Karp B, et al. 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.Google Scholar
  31. 31.
    Elneihoum AM, Falke P, Axelsson L, et al. Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. Stroke 1996, 27: 1734–8.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2004

Authors and Affiliations

  • A. Szczudlik
    • 1
  • T. Dziedzic
    • 1
  • S. Bartus
    • 2
  • A. Slowik
    • 1
  • A. Kieltyka
    • 3
  1. 1.Department of NeurologyJagiellonian UniversityKrakowPoland
  2. 2.2nd Department of CardiologyJagiellonian UniversityKrakowPoland
  3. 3.Department of Epidemiology, Collegium MedicumJagiellonian UniversityKrakowPoland

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