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

α-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 α-MSH inhibits nitric oxide (NO) production in cultured macrophages. To determine how α-MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum. α-MSH prevented liver inflammation even when given 30 min after LPS administration. To determine the mechanisms of action of α-MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines. α-MSH inhibited systemic NO production, hepatic neutropHil infiltration, and increased hepatic mRNA abundance for TNFα, and the neutropHil and monocyte chemokines (KC/IL-8 and MCP-1). We conclude that α- MSH prevents LPS-induced hepatic inflammation by inhibiting production of chemoattractant chemokines which then modulate infiltration of inflammatory cells. Thus, α-MSH has an effect very early in the inflammatory cascade.