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. 1990 Mar;79(3):470–473. doi: 10.1111/j.1365-2249.1990.tb08114.x

Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells.

M A Salas 1, S W Evans 1, M J Levell 1, J T Whicher 1
PMCID: PMC1534960  PMID: 2156641

Abstract

We investigated whether interleukin-6 (IL-6) could cause the release of corticosterone by a direct interaction with the adrenal gland. Primary cultures of rat adrenal glands were obtained by dispersion with collagenase and incubated for 24 h with different doses of IL-6. Levels of corticosterone were measured by competitive protein binding assay. A significant (P less than 0.025) dose-dependent increase in corticosterone levels was seen at all doses used. Time course experiments demonstrated that IL-6 stimulated corticosterone release over a period of 24 h but not after 12 or 3 h. The stimulation of adrenal cells with different doses of ACTH1-24 and 40 U/ml of IL-6 showed a synergistic effect when IL-6 was combined with low concentrations of ACTH1-24 (2 and 20 pmol/l). This effect was not evident at higher doses. Our results suggest that IL-6 may act at different levels of the hypothalmic pituitary adrenal axis. Moreover the finding of a synergistic effect with ACTH1-24 indicates that IL-6 could play a role in the long term response to stress.

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Selected References

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  1. Bernton E. W., Beach J. E., Holaday J. W., Smallridge R. C., Fein H. G. Release of multiple hormones by a direct action of interleukin-1 on pituitary cells. Science. 1987 Oct 23;238(4826):519–521. doi: 10.1126/science.2821620. [DOI] [PubMed] [Google Scholar]
  2. Besedovsky H., Sorkin E., Keller M., Müller J. Changes in blood hormone levels during the immune response. Proc Soc Exp Biol Med. 1975 Nov;150(2):466–470. doi: 10.3181/00379727-150-39057. [DOI] [PubMed] [Google Scholar]
  3. Besedovsky H., del Rey A., Sorkin E., Dinarello C. A. Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science. 1986 Aug 8;233(4764):652–654. doi: 10.1126/science.3014662. [DOI] [PubMed] [Google Scholar]
  4. Castell J. V., Gómez-Lechón M. J., David M., Hirano T., Kishimoto T., Heinrich P. C. Recombinant human interleukin-6 (IL-6/BSF-2/HSF) regulates the synthesis of acute phase proteins in human hepatocytes. FEBS Lett. 1988 May 23;232(2):347–350. doi: 10.1016/0014-5793(88)80766-x. [DOI] [PubMed] [Google Scholar]
  5. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Helle M., Brakenhoff J. P., De Groot E. R., Aarden L. A. Interleukin 6 is involved in interleukin 1-induced activities. Eur J Immunol. 1988 Jun;18(6):957–959. doi: 10.1002/eji.1830180619. [DOI] [PubMed] [Google Scholar]
  7. Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6;324(6092):73–76. doi: 10.1038/324073a0. [DOI] [PubMed] [Google Scholar]
  8. Kehrer P., Turnill D., Dayer J. M., Muller A. F., Gaillard R. C. Human recombinant interleukin-1 beta and -alpha, but not recombinant tumor necrosis factor alpha stimulate ACTH release from rat anterior pituitary cells in vitro in a prostaglandin E2 and cAMP independent manner. Neuroendocrinology. 1988 Aug;48(2):160–166. doi: 10.1159/000125004. [DOI] [PubMed] [Google Scholar]
  9. Lee S. W., Tsou A. P., Chan H., Thomas J., Petrie K., Eugui E. M., Allison A. C. Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1204–1208. doi: 10.1073/pnas.85.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Murphy B. E. Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab. 1967 Jul;27(7):973–990. doi: 10.1210/jcem-27-7-973. [DOI] [PubMed] [Google Scholar]
  11. Naitoh Y., Fukata J., Tominaga T., Nakai Y., Tamai S., Mori K., Imura H. Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1459–1463. doi: 10.1016/s0006-291x(88)81305-6. [DOI] [PubMed] [Google Scholar]
  12. Nijsten M. W., de Groot E. R., ten Duis H. J., Klasen H. J., Hack C. E., Aarden L. A. Serum levels of interleukin-6 and acute phase responses. Lancet. 1987 Oct 17;2(8564):921–921. doi: 10.1016/s0140-6736(87)91413-9. [DOI] [PubMed] [Google Scholar]
  13. Ramadori G., Van Damme J., Rieder H., Meyer zum Büschenfelde K. H. Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. Eur J Immunol. 1988 Aug;18(8):1259–1264. doi: 10.1002/eji.1830180817. [DOI] [PubMed] [Google Scholar]
  14. Roh M. S., Drazenovich K. A., Barbose J. J., Dinarello C. A., Cobb C. F. Direct stimulation of the adrenal cortex by interleukin-1. Surgery. 1987 Aug;102(2):140–146. [PubMed] [Google Scholar]
  15. Sapolsky R., Rivier C., Yamamoto G., Plotsky P., Vale W. Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science. 1987 Oct 23;238(4826):522–524. doi: 10.1126/science.2821621. [DOI] [PubMed] [Google Scholar]
  16. Snyder D. S., Unanue E. R. Corticosteroids inhibit murine macrophage Ia expression and interleukin 1 production. J Immunol. 1982 Nov;129(5):1803–1805. [PubMed] [Google Scholar]
  17. Tsagarakis S., Gillies G., Rees L. H., Besser M., Grossman A. Interleukin-1 directly stimulates the release of corticotrophin releasing factor from rat hypothalamus. Neuroendocrinology. 1989 Jan;49(1):98–101. doi: 10.1159/000125096. [DOI] [PubMed] [Google Scholar]
  18. Vaughan G. M., Becker R. A., Allen J. P., Goodwin C. W., Jr, Pruitt B. A., Jr, Mason A. D., Jr Cortisol and corticotrophin in burned patients. J Trauma. 1982 Apr;22(4):263–273. doi: 10.1097/00005373-198204000-00001. [DOI] [PubMed] [Google Scholar]
  19. Walker S. W., Lightly E. R., Milner S. W., Williams B. C. Catecholamine stimulation of cortisol secretion by 3-day primary cultures of purified zona fasciculata/reticularis cells isolated from bovine adrenal cortex. Mol Cell Endocrinol. 1988 May;57(1-2):139–147. doi: 10.1016/0303-7207(88)90043-3. [DOI] [PubMed] [Google Scholar]
  20. Walther Z., May L. T., Sehgal P. B. Transcriptional regulation of the interferon-beta 2/B cell differentiation factor BSF-2/hepatocyte-stimulating factor gene in human fibroblasts by other cytokines. J Immunol. 1988 Feb 1;140(3):974–977. [PubMed] [Google Scholar]
  21. Whitcomb R. W., Linehan W. M., Wahl L. M., Knazek R. A. Monocytes stimulate cortisol production by cultured human adrenocortical cells. J Clin Endocrinol Metab. 1988 Jan;66(1):33–38. doi: 10.1210/jcem-66-1-33. [DOI] [PubMed] [Google Scholar]
  22. Woloski B. M., Smith E. M., Meyer W. J., 3rd, Fuller G. M., Blalock J. E. Corticotropin-releasing activity of monokines. Science. 1985 Nov 29;230(4729):1035–1037. doi: 10.1126/science.2997929. [DOI] [PubMed] [Google Scholar]

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