Alpha-melanocyte-stimulating hormone suppresses antigen-stimulated T cell production of gamma-interferon

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) is known to suppress cytokine-mediated inflammation. In addition, we previously found that alpha-MSH suppressed the production of the proinflammatory cytokine interferon (IFN)-gamma by antigen-stimulated primed lymph node T cells. This immunosuppressive activity of alpha-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 alpha-MSH, antigen-stimulated lymph node T cell cultures were treated with alpha-MSH in the presence of neutralizing anti-IL-4 antibodies. The enhanced production of IFN-gamma caused by the presence of anti-IL-4 alone in the T cell cultures was squelched by alpha-MSH. This demonstrated that in these cultures, alpha-MSH regulation of IFN-gamma 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 alpha-MSH down-regulation of IFN-gamma production, and the addition of alpha-MSH to IL-4-treated cultures did not further depress IFN-gamma production. These and the previous results suggest that the mechanism of alpha-MSH suppression of IFN-gamma 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 alpha-MSH, there was a significant reduction (60-70%) of APC elicitation of IFN-gamma production by untreated primed T cells.(ABSTRACT TRUNCATED AT 250 WORDS)