Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Aug;90(2):596–603. doi: 10.1172/JCI115898

Endogenous cortisol regulates immunoglobulin E-dependent late phase reactions.

R F Herrscher 1, C Kasper 1, T J Sullivan 1
PMCID: PMC443138  PMID: 1644926

Abstract

To investigate the impact that physiological variation in serum cortisol has on IgE-mediated events, 10 atopic subjects underwent cutaneous antigen challenge with measurement of the early phase wheal (EPW) at 20 min and the late phase reaction (LPR) at 6 h. All subjects were challenged during control conditions between 8:00 and 9:00 a.m. Repeat challenges were performed in five subjects at 6:00 p.m. and in eight subjects after ingestion of metyrapone, a specific inhibitor of cortisol synthesis. Compared with control values, mean serum cortisol was suppressed in the evening and after metyrapone (P less than 0.05 all time points). No effect was seen on the EPW, but mean LPR diameters at three antigen dilutions were significantly increased by cortisol suppression (P less than 0.05). Replacement doses of hydrocortisone given in the evening and with metyrapone abrogated these increases. Blinded analysis of LPR biopsies from cortisol-suppressed subjects revealed increases in leukocytoclasis (P less than or equal to 0.0001), interstitial leukocytes (P less than or equal to 0.01), and eosinophils (P less than or equal to 0.04). These results indicate that physiological levels of serum cortisol can regulate IgE-dependent cutaneous inflammation by affecting the expression of cellular events at late phase sites.

Full text

PDF
596

Images in this article

600Image
on p.600

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Almawi W. Y., Lipman M. L., Stevens A. C., Zanker B., Hadro E. T., Strom T. B. Abrogation of glucocorticoid-mediated inhibition of T cell proliferation by the synergistic action of IL-1, IL-6, and IFN-gamma. J Immunol. 1991 May 15;146(10):3523–3527. [PubMed] [Google Scholar]
  2. Atkins P., Green G. R., Zweiman B. Histologic studies of human skin test responses to ragweed, compound 48-80, and histamine. J Allergy Clin Immunol. 1973 May;51(5):263–273. doi: 10.1016/0091-6749(73)90128-0. [DOI] [PubMed] [Google Scholar]
  3. Barnes P., FitzGerald G., Brown M., Dollery C. Nocturnal asthma and changes in circulating epinephrine, histamine, and cortisol. N Engl J Med. 1980 Jul 31;303(5):263–267. doi: 10.1056/NEJM198007313030506. [DOI] [PubMed] [Google Scholar]
  4. Beasley R., Roche W. R., Roberts J. A., Holgate S. T. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis. 1989 Mar;139(3):806–817. doi: 10.1164/ajrccm/139.3.806. [DOI] [PubMed] [Google Scholar]
  5. Berkenbosch F., van Oers J., del Rey A., Tilders F., Besedovsky H. Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science. 1987 Oct 23;238(4826):524–526. doi: 10.1126/science.2443979. [DOI] [PubMed] [Google Scholar]
  6. Bernardini R., Kamilaris T. C., Calogero A. E., Johnson E. O., Gomez M. T., Gold P. W., Chrousos G. P. Interactions between tumor necrosis factor-alpha, hypothalamic corticotropin-releasing hormone, and adrenocorticotropin secretion in the rat. Endocrinology. 1990 Jun;126(6):2876–2881. doi: 10.1210/endo-126-6-2876. [DOI] [PubMed] [Google Scholar]
  7. Besedovsky H. O., Del Rey A., Sorkin E. Antigenic competition between horse and sheep red blood cells as a hormone-dependent phenomenon. Clin Exp Immunol. 1979 Jul;37(1):106–113. [PMC free article] [PubMed] [Google Scholar]
  8. Besedovsky H. O., del Rey A., Sorkin E. Lymphokine-containing supernatants from con A-stimulated cells increase corticosterone blood levels. J Immunol. 1981 Jan;126(1):385–387. [PubMed] [Google Scholar]
  9. Britton S., Thorén M., Sjoberg H. E. The immunological hazard of Cushing's syndrome. Br Med J. 1975 Dec 20;4(5998):678–680. doi: 10.1136/bmj.4.5998.678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bruno O. D., Leclerq R., Virasoro E., Copinschi G. Extra-adrenal actions of metyrapone in man. Effects on plasma cortisol disappearance, growth hormone secretion and glucose metabolism. J Clin Endocrinol Metab. 1971 Feb;32(2):260–265. doi: 10.1210/jcem-32-2-260. [DOI] [PubMed] [Google Scholar]
  11. Canalis E., Caldarella A. M., Reardon G. E. Serum cortisol and 11 deoxycortisol by liquid chromatography: clinical studies and comparison with radioimmunoassay. Clin Chem. 1979 Oct;25(10):1700–1703. [PubMed] [Google Scholar]
  12. Charlesworth E. N., Kagey-Sobotka A., Schleimer R. P., Norman P. S., Lichtenstein L. M. Prednisone inhibits the appearance of inflammatory mediators and the influx of eosinophils and basophils associated with the cutaneous late-phase response to allergen. J Immunol. 1991 Jan 15;146(2):671–676. [PubMed] [Google Scholar]
  13. Clark T. J., Hetzel M. R. Diurnal variation of asthma. Br J Dis Chest. 1977 Apr;71(2):87–92. doi: 10.1016/0007-0971(77)90087-0. [DOI] [PubMed] [Google Scholar]
  14. Cohan V. L., Undem B. J., Fox C. C., Adkinson N. F., Jr, Lichtenstein L. M., Schleimer R. P. Dexamethasone does not inhibit the release of mediators from human mast cells residing in airway, intestine, or skin. Am Rev Respir Dis. 1989 Oct;140(4):951–954. doi: 10.1164/ajrccm/140.4.951. [DOI] [PubMed] [Google Scholar]
  15. Dolovich J., Hargreave F. E., Chalmers R., Shier K. J., Gauldie J., Bienenstock J. Late cutaneous allergic responses in isolated IgE-dependent reactions. J Allergy Clin Immunol. 1973 Jul;52(1):38–46. doi: 10.1016/0091-6749(73)90119-x. [DOI] [PubMed] [Google Scholar]
  16. Dorsch W., Ring J. Induction of late cutaneous reactions by skin-blister fluid from allergen-tested and normal skin. J Allergy Clin Immunol. 1981 Feb;67(2):117–123. doi: 10.1016/0091-6749(81)90006-3. [DOI] [PubMed] [Google Scholar]
  17. Frew A. J., Kay A. B. The relationship between infiltrating CD4+ lymphocytes, activated eosinophils, and the magnitude of the allergen-induced late phase cutaneous reaction in man. J Immunol. 1988 Dec 15;141(12):4158–4164. [PubMed] [Google Scholar]
  18. Gordon J. R., Burd P. R., Galli S. J. Mast cells as a source of multifunctional cytokines. Immunol Today. 1990 Dec;11(12):458–464. doi: 10.1016/0167-5699(90)90176-a. [DOI] [PubMed] [Google Scholar]
  19. Gordon J. R., Galli S. J. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature. 1990 Jul 19;346(6281):274–276. doi: 10.1038/346274a0. [DOI] [PubMed] [Google Scholar]
  20. Grönneberg R., Strandberg K., Stålenheim G., Zetterström O. Effect in man of anti-allergic drugs on the immediate and late phase cutaneous allergic reactions induced by anti-IgE. Allergy. 1981 Apr;36(3):201–208. doi: 10.1111/j.1398-9995.1981.tb01835.x. [DOI] [PubMed] [Google Scholar]
  21. Gurish M. F., Ghildyal N., Arm J., Austen K. F., Avraham S., Reynolds D., Stevens R. L. Cytokine mRNA are preferentially increased relative to secretory granule protein mRNA in mouse bone marrow-derived mast cells that have undergone IgE-mediated activation and degranulation. J Immunol. 1991 Mar 1;146(5):1527–1533. [PubMed] [Google Scholar]
  22. INGLE D. J. The role of the adrenal cortex in homeostasis. J Endocrinol. 1952 Oct;8(4):xxiii–xxxvii. [PubMed] [Google Scholar]
  23. Jensen H. K., Blichert-Toft M. Investigation of pituitary-adrenocortical function in the elderly during standardized operations and postoperative intravenous metyrapone test assessed by plasma cortisol, plasma compound S and eosinophil cell determinations. Acta Endocrinol (Copenh) 1971 Jul;67(3):495–507. doi: 10.1530/acta.0.0670495. [DOI] [PubMed] [Google Scholar]
  24. Kallenbach J. M., Panz V. R., Joffe B. I., Jankelow D., Anderson R., Haitas B., Seftel H. C. Nocturnal events related to "morning dipping" in bronchial asthma. Chest. 1988 Apr;93(4):751–757. doi: 10.1378/chest.93.4.751. [DOI] [PubMed] [Google Scholar]
  25. LIDDLE G. W., ISLAND D., LANCE E. M., HARRIS A. P. Alterations of adrenal steroid patterns in man resulting from treatment with a chemical inhibitor of 11 beta-hydroxylation. J Clin Endocrinol Metab. 1958 Aug;18(8):906–912. doi: 10.1210/jcem-18-8-906. [DOI] [PubMed] [Google Scholar]
  26. Lee R. E., Smolensky M. H., Leach C. S., McGovern J. P. Circadian rhythms in the cutaneous reactivity to histamine and selected antigens, including phase relationship to urinary cortisol excretion. Ann Allergy. 1977 Apr;38(4):231–236. [PubMed] [Google Scholar]
  27. Lemanske R. F., Jr, Kaliner M. Late-phase IgE-mediated reactions. J Clin Immunol. 1988 Jan;8(1):1–13. doi: 10.1007/BF00915151. [DOI] [PubMed] [Google Scholar]
  28. MANCINI R. E., COLOMBI P. A., GALLI H., ORCIUOLI L. Effect of glucocorticoid hormones on experimentally induced allergic reactions on human skin. A histologic and histochemical study. J Allergy. 1961 Nov-Dec;32:471–482. doi: 10.1016/0021-8707(61)90001-6. [DOI] [PubMed] [Google Scholar]
  29. Mohiuddin A. A., Martin R. J. Circadian basis of the late asthmatic response. Am Rev Respir Dis. 1990 Nov;142(5):1153–1157. doi: 10.1164/ajrccm/142.5.1153. [DOI] [PubMed] [Google Scholar]
  30. Munck A., Guyre P. M., Holbrook N. J. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984 Winter;5(1):25–44. doi: 10.1210/edrv-5-1-25. [DOI] [PubMed] [Google Scholar]
  31. Nakazawa T., Toyoda T., Furukawa M., Taya T., Kobayashi S. Inhibitory effects of various drugs on dual asthmatic responses in wheat flour-sensitive subjects. J Allergy Clin Immunol. 1976 Jul;58(1 Pt 1):1–9. doi: 10.1016/0091-6749(76)90101-9. [DOI] [PubMed] [Google Scholar]
  32. Navarra P., Tsagarakis S., Faria M. S., Rees L. H., Besser G. M., Grossman A. B. Interleukins-1 and -6 stimulate the release of corticotropin-releasing hormone-41 from rat hypothalamus in vitro via the eicosanoid cyclooxygenase pathway. Endocrinology. 1991 Jan;128(1):37–44. doi: 10.1210/endo-128-1-37. [DOI] [PubMed] [Google Scholar]
  33. Patt J. A., Jr, Eberhart R. J. Total and differential leukocyte counts in cesarean-derived newborn pigs following treatment with ACTH or metyrapone. Am J Vet Res. 1977 Jun;38(6):793–797. [PubMed] [Google Scholar]
  34. Pipkorn U., Proud D., Lichtenstein L. M., Schleimer R. P., Peters S. P., Adkinson N. F., Jr, Kagey-Sobotka A., Norman P. S., Naclerio R. M. Effect of short-term systemic glucocorticoid treatment on human nasal mediator release after antigen challenge. J Clin Invest. 1987 Oct;80(4):957–961. doi: 10.1172/JCI113188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  36. Poothullil J., Umemoto L., Dolovich J., Hargreave F. E., Day R. P. Inhibition by prednisone of late cutaneous allergic responses induced by antiserum to human IgE. J Allergy Clin Immunol. 1976 Feb;57(2):164–167. doi: 10.1016/0091-6749(76)90035-x. [DOI] [PubMed] [Google Scholar]
  37. REINBERG A., GHATA J., SIDI E. CIRCADIAN REACTIVITY RHYTHMS OF HUMAN SKIN TO HISTAMINE OR ALLERGEN AND THE ADRENAL CYCLE. J Allergy. 1965 May-Jun;36:273–283. doi: 10.1016/0021-8707(65)90086-9. [DOI] [PubMed] [Google Scholar]
  38. Reed C. E. Basic mechanisms of asthma. Role of inflammation. Chest. 1988 Jul;94(1):175–177. doi: 10.1378/chest.94.1.175. [DOI] [PubMed] [Google Scholar]
  39. Reinberg A., Gervais P., Levi F., Smolensky M., Del Cerro L., Ugolini C. Circadian and circannual rhythms of allergic rhinitis: an epidemiologic study involving chronobiologic methods. J Allergy Clin Immunol. 1988 Jan;81(1):51–62. doi: 10.1016/0091-6749(88)90220-5. [DOI] [PubMed] [Google Scholar]
  40. Richerson H. B., Rajtora D. W., Penick G. D., Dick F. R., Yoo T. J., Kammermeyer J. K., Anuras J. S. Cutaneous and nasal allergic responses in ragweed hay fever: lack of clinical and histopathologic correlations with late phase reactions. J Allergy Clin Immunol. 1979 Jul;64(1):67–77. doi: 10.1016/0091-6749(79)90085-x. [DOI] [PubMed] [Google Scholar]
  41. Rothwell P. M., Udwadia Z. F., Lawler P. G. Cortisol response to corticotropin and survival in septic shock. Lancet. 1991 Mar 9;337(8741):582–583. doi: 10.1016/0140-6736(91)91641-7. [DOI] [PubMed] [Google Scholar]
  42. SAYERS G. The adrenal cortex and homoestasis. Physiol Rev. 1950 Jul;30(3):241–320. doi: 10.1152/physrev.1950.30.3.241. [DOI] [PubMed] [Google Scholar]
  43. Sasaki H., Yanai M., Shimura S., Okayama H., Aikawa T., Sasaki T., Takishima T. Late asthmatic response to Ascaris antigen challenge in dogs treated with metyrapone. Am Rev Respir Dis. 1987 Dec;136(6):1459–1465. doi: 10.1164/ajrccm/136.6.1459. [DOI] [PubMed] [Google Scholar]
  44. Schleimer R. P. Effects of glucocorticosteroids on inflammatory cells relevant to their therapeutic applications in asthma. Am Rev Respir Dis. 1990 Feb;141(2 Pt 2):S59–S69. [PubMed] [Google Scholar]
  45. Solley G. O., Gleich G. J., Jordon R. E., Schroeter A. L. The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies. J Clin Invest. 1976 Aug;58(2):408–420. doi: 10.1172/JCI108485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Soutar C. A., Costello J., Ijaduola O., Turner-Warwick M. Nocturnal and morning asthma. Relationship to plasma corticosteroids and response to cortisol infusion. Thorax. 1975 Aug;30(4):436–440. doi: 10.1136/thx.30.4.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sternberg E. M., Hill J. M., Chrousos G. P., Kamilaris T., Listwak S. J., Gold P. W., Wilder R. L. Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2374–2378. doi: 10.1073/pnas.86.7.2374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Thornhill M. H., Haskard D. O. IL-4 regulates endothelial cell activation by IL-1, tumor necrosis factor, or IFN-gamma. J Immunol. 1990 Aug 1;145(3):865–872. [PubMed] [Google Scholar]
  49. Turner-Warwick M. Epidemiology of nocturnal asthma. Am J Med. 1988 Jul 29;85(1B):6–8. doi: 10.1016/0002-9343(88)90231-8. [DOI] [PubMed] [Google Scholar]
  50. Umemoto L., Poothullil J., Dolovich J., Hargreave F. E. Factors which influence late cutaneous allergic responses. J Allergy Clin Immunol. 1976 Jul;58(1 Pt 1):60–68. doi: 10.1016/0091-6749(76)90107-x. [DOI] [PubMed] [Google Scholar]
  51. Vichyanond P., Nelson H. S. Circadian variation of skin reactivity and allergy skin tests. J Allergy Clin Immunol. 1989 Jun;83(6):1101–1106. doi: 10.1016/0091-6749(89)90452-1. [DOI] [PubMed] [Google Scholar]
  52. Wardlaw A. J., Dunnette S., Gleich G. J., Collins J. V., Kay A. B. Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Relationship to bronchial hyperreactivity. Am Rev Respir Dis. 1988 Jan;137(1):62–69. doi: 10.1164/ajrccm/137.1.62. [DOI] [PubMed] [Google Scholar]
  53. Weitzman E. D., Fukushima D., Nogeire C., Roffwarg H., Gallagher T. F., Hellman L. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab. 1971 Jul;33(1):14–22. doi: 10.1210/jcem-33-1-14. [DOI] [PubMed] [Google Scholar]
  54. Weller F. R., Weller H. H., Kallenberg C. G., The T. H., Orie N. G. Sensitivity to hydrocortisone is a relevant factor in the immunoendocrine relationship. I. The cell-mediated immune response in relation to blood levels and in vitro immunosuppressive effects of hydrocortisone in patients with asthma and healthy control subjects. J Allergy Clin Immunol. 1986 Sep;78(3 Pt 1):423–430. doi: 10.1016/0091-6749(86)90028-x. [DOI] [PubMed] [Google Scholar]
  55. deShazo R. D., Levinson A. I., Dvorak H. F., Davis R. W. The late phase skin reaction: evidence for activation of the coagulation system in an IgE-dependent reaction in man. J Immunol. 1979 Feb;122(2):692–698. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES