Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation

J Clin Invest. 1996 May 1;97(9):2038-44. doi: 10.1172/JCI118639.

Abstract

Alpha-Melanocyte-stimulating hormone (MSH) is a potent anti-inflammatory 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 macro-phages. 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-1). 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury
  • Female
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Lipopolysaccharides / toxicity*
  • Liver Diseases / metabolism
  • Liver Diseases / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Propionibacterium acnes
  • alpha-MSH / administration & dosage*

Substances

  • Lipopolysaccharides
  • Nitric Oxide
  • alpha-MSH