Interleukin-1 and interleukin-6 act synergistically to stimulate the release of adrenocorticotropic hormone in vivo.

Interleukin-1 (IL-1) and interleukin-6 (IL-6) share a number of biological functions. Because IL-1 induces IL-6 in vivo, the extent to which IL-6 mediates the effects of IL-1 has come under investigation. The stimulation of the hypothalamic-pituitary-adrenal axis by IL-1 and IL-6 is a critical component of the inflammatory response. The present study was designed to compare the effects of recombinant human IL-1 alpha (rhIL-1 alpha) and recombinant human IL-6 (rhIL-6) administered in combination and alone on the release of adrenocorticotropic hormone (ACTH) in mice. We have demonstrated that the administration of rhIL-6 alone does not duplicate the stimulatory effect of rhIL-1 alpha on ACTH release. On the other hand, suboptimal amounts of rhIL-1 alpha and rhIL-6 synergize to induce an early (30-60 min) ACTH response and produce a later (2-3 h) response that is similar to the one observed after rhIL-1 alpha is administered alone. These results suggest that the 2-3 h response to rhIL-1 alpha may be dependent on synergy with the endogenous IL-6 it induces systemically and in the central nervous system (including the hypothalamus and the pituitary gland).