α Melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1

The ability of interleukin 1 (IL 1) to augment the proliferation of murine thymocytes in vitro was inhibited in a dose-dependent manner by the neuropeptide α-melanocyte-stimulating hormone (αMSH). The minimal effective concentration of αMSH was 10^-11 M. Maximal effect occurred between 10^-8 and 10^-7 M, with diminishing effectiveness at higher concentrations. IL 1-induced production of prostaglandin E (PGE) by fibroblasts was also inhibited by αMSH with a biphasic dose response. The minimal effective concentration was 10^-11 M, and maximum effect was achieved at 10^-10 M. αMSH appeared to affect the interaction of IL 1 with its target cells in a specific manner, because it did not inhibit basal mitogen-induced thymocyte proliferation or IL 2-induced proliferation of a cytotoxic T lymphocyte line. Furthermore, production of IL 1 by endotoxin-stimulated monocytes was not affected by αMSH. An analog of αMSH (Nle⁴,D-Phe⁷αMSH), which is highly potent in other melanotropin-sensitive systems, did not affect the action of IL 1 on thymocytes, suggesting that the immunomodulatory effects of αMSH may not be mediated by the classic melanocyte αMSH receptor. The influence of αMSH on thymocytes and fibroblasts suggests that αMSH is an endogenous antagonist of IL 1, perhaps important for limiting inflammatory damage to host tissues.