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

Chiao H, Foster S, Thomas R +2 more1996Journal of Clinical InvestigationJournal Article
10.1172/jci118639PubMedFree full text
Endocrine (ADH/ACTH/MSH)Immune/Innate
Bacterial Endotoxins

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.

Cited By (24)

  • Targeting melanocortin receptors as a novel strategy to control inflammationPharmacological Reviews · 2004
  • Anti-inflammatory actions of the neuroimmunomodulator α-MSHImmunology Today · 1997
  • α-Melanocyte-Stimulating Hormone and Related Tripeptides: Biochemistry, Antiinflammatory and Protective Effects in Vitro and in Vivo, and Future Perspectives for the Treatment of Immune-Mediated Inflammatory DiseasesEndocrine Reviews
  • In vitro induction of CD25+ CD4+ regulatory T cells by the neuropeptide alpha‐melanocyte stimulating hormone (α‐MSH)Immunology and Cell Biology · 2001
  • α-Melanocyte-stimulating Hormone Inhibits Lipopolysaccharide-induced Tumor Necrosis Factor-α Production in Leukocytes by Modulating Protein Kinase A, p38 Kinase, and Nuclear Factor κB Signaling PathwaysJournal of Biological Chemistry · 2003
  • Mechanisms of Antiinflammatory Action of the Neuroimmunomodulatory Peptide α‐MSHAnnals of the New York Academy of Sciences · 1998

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