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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< 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.