Regulation of the in vitro antibody response by neuroendocrine hormones.

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 (>/=80% suppression) of the antibody response to the T-cell-dependent antigen sheep erythrocytes at a concentration of 0.5 muM. [Met]- and [Leu]enkephalin were moderate inhibitors (approximately 60% suppression) at 0.2-2 muM, and beta- and gamma-endorphin were minimal inhibitors (approximately 20% suppression) at 5-6 muM. 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; thus, 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. The data show that neuroendocrine polypeptide hormones can regulate the immune response.