Regulation of the in vitro antibody response by neuroendocrine hormones

Abstract

Treatment of lymphocytes with inducers of interferon .alpha. (IFN-.alpha.) results in the production of corticotropin (ACTH) and endorphin-like activities. The pro-opiomelanocortin-derived hormones ACTH and .alpha.-, .beta.- and .gamma.-endorphin and the structurally related hormones [Leu]- and [Met]enkephalin were therefore tested for their effects on the in vitro antibody response of mouse spleen cells. ACTH and .alpha.-endorphin were potent inhibitors (.gtoreq. 80% suppression) of the antibody response to the T-cell-dependent antigen sheep erythrocytes at a concentration of 0.5 .mu.M. [Met]- and [Leu]enkephalin were moderate inhibitors (.apprx. 60% suppression) at 0.2-2 .mu.M, and .beta.- and .gamma.-endorphin were minimal inhibitors (.apprx. 20% suppression) at 5-6 .mu.M. At higher concentrations ACTH also inhibited the antibody response to the T-cell-independent antigen dinitrophenyl Ficoll, suggesting that T-cell function was more sensitive to blockage by these hormones than was B-cell function. ACTH and IFN had similar suppression properties; the hormone-like activities associated with IFN-.alpha. may play a role in IFN-induced immunosuppression. .alpha.-Endorphin immunosuppression was blocked by naloxone, which suggested that .alpha.-endorphin exerted its effects through binding to opiate-like receptors on the spleen cells. The failure of .beta.-endorphin to suppress the immune response significantly was not due to its failure to bind to the opiate-like receptors because it blocked .alpha.-endorphin-induced suppression. Direct evidence for both opiate and ACTH receptors on the spleen cells was obtained in binding studies with labeled enkephalin and ACTH. Such studies revealed the presence of both high- and low-affinity receptors. Neuroendocrine polypeptide hormones can regulate the immune response.