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

Hsi Chiao, Steve Foster, Robyn Thomas, James Lipton, Robert A. Star

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2038-2044
Number of pages7
JournalJournal of Clinical Investigation
Volume97
Issue number9
DOIs
StatePublished - May 1 1996

Keywords

  • KC/IL-8
  • MCP-1
  • TNFα
  • neutrophils
  • nitric oxide

ASJC Scopus subject areas

  • Medicine(all)

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