Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.
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.
Chiao
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H
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Foster
S
S
Thomas
R
R
Lipton
J
J
Star
R A
RA
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000633:toxicity*; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D011425:Propionibacterium acnes; D000521:alpha-MSH / Q000008:administration & dosage*
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000521:alpha-MSH