Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells.
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.
Salas
M A
MA
Department of Chemical Pathology, Old Medical School, University of Leeds, England.
Evans
S W
SW
Levell
M J
MJ
Whicher
J T
JT
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D015850:Interleukin-6; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone