Abstract
Since alpha-MSH suppresses endotoxin-induced inflammation by innate immunity, it is possible that alpha-MSH can suppress the interface between innate and adaptive immunity mediated by TLR4-stimulated macrophages. Endotoxin-stimulated macrophages treated with alpha-MSH are suppressed in nitric oxide and IL-12p70 production, and cannot enhance antigen-stimulated IFN-gamma production by Th1 cells. In macrophages treated with alpha-MSH, the inhibitory molecule IRAK-M is bound to IRAK-1, the proximal intracellular signal molecule of endotoxin-bound TLR4. These results further demonstrate the dynamic contribution of the nervous system, and the role of alpha-MSH in modulating the innate and adaptive immune interface in an inflammatory response.