alpha-Melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation

alpha-Melanocyte-stimulating hormone (MSH) is a potent antiinflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation, We showed previously that alpha-MSH inhibits nitric oxide (NO) production in cultured macrophages, To determine how alpha-MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum. alpha-MSH prevented liver inflammation even when given 30 min after LPS administration, To determine the mechanisms of action of alpha-MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines. alpha-MSH inhibited systemic NO production, hepatic neutrophil infiltration, and increased hepatic mRNA abundance for TNF alpha, and the neutrophil and monocyte chemokines (KC/IL-8 and MCP-I). We conclude that alpha-MSH prevents LPS-induced hepatic inflammation by inhibiting production of chemoattractant chemokines which then modulate infiltration of inflammatory cells, Thus, alpha-MSH has an effect very early in the inflammatory cascade.