Alpha-Melanocyte-Stimulating Hormone Suppresses Antigen-Stimulated T Cell Production of Gamma-lnterferon

The neuropeptide Α-melanocyte-stimulating hormone (Α-MSH) is known to suppress cytokine-mediated inflammation. In addition, we previously found that Α-MSH suppressed the production of the proinflammatory cytokine interferon (IFN)-Γ by antigen-stimulated primed lymph node T cells. This immunosuppressive activity of Α-MSH on lymph node T cell cultures is similar to that of interleukin (IL)-4. To further examine the potential ‘IL-4 like’ activities of Α-MSH, antigen-stimulated lymph node T cell cultures were treated with Α-MSH in the presence of neutralizing anti-IL-4 antibodies. The enhanced production of IFN-Γ caused by the presence of anti-IL-4 alone in the T cell cultures was squelched by Α-MSH. This demonstrated that in these cultures, Α-MSH regulation of IFN-Γ production operates in a fashion similar to that of endogenous IL-4. Addition of exogenous IL-4 to antigen-stimulated lymph node T cell cultures did not intensify Α-MSH down-regulation of IFN-Γ production, and the addition of Α-MSH to IL-4-treated cultures did not further depress IFN-Γ production. These and the previous results suggest that the mechanism of Α-MSH suppression of IFN-Γ production in the antigen-stimulated T cell cultures is similar to, but independent of, IL-4. When antigen-presenting cells (APCs) were the only cells in the antigen-stimulated T cell cultures treated with a-MSH, there was a significant reduction (60-70%) of APC elicitation of IFN-y production by untreated primed T cells. Moreover, Α-MSH prevented IFN-Γ production by 80-100% when primed T cells were the only cells treated with a-MSH. The mechanism of a-MSH prevention of antigen-stimulated IFN-Γ production in T cell cultures involves both APC and primed T cells. Since Α-MSH is constitutively present in the skin, serum, brain and eye, this neuropeptide may play an important immunomodulatory role linking the nervous system and the rest of the body. In particular, Α-MSH may be critical to the phenomenon of immune privilege in the eye and brain.