Inhibition of Systemic Inflammation by Central Action of the Neuropeptide α-Melanocyte- Stimulating Hormone
Abstract
The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central alpha-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-alpha and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Lung myeloperoxidase activity, a marker of neutrophil infiltration, was increased in endotoxemic mice; the increase was significantly less in lungs of mice treated with central alpha-MSH. Intraperitoneal administration of the small dose of alpha-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central alpha-MSH, we tested the idea that endogenous peptide induced within the brain during systemic inflammation modulates host responses to endotoxic challenge in peripheral tissues. The data showed that proinflammatory agents induced by endotoxin in the circulation, lungs, and liver were significantly greater after blockade of central alpha-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation.
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Cited By (8)
- Targeting melanocortin receptors as a novel strategy to control inflammationPharmacological Reviews · 2004
- α‐MSH in Systemic Inflammation: Central and Peripheral ActionsAnnals of the New York Academy of Sciences · 1999
- PRODUCTION AND EFFECTS OF α-MELANOCYTE-STIMULATING HORMONE DURING ACUTE LUNG INJURYShock · 2007
- α-Melanocyte-Stimulating Hormone Is Decreased in Plasma of Patients with Acute Brain InjuryJournal of Neurotrauma · 2003
- Plasma concentrations and anti-L-cytokine effects of α-melanocyte stimulating hormone in septic patientsCritical Care Medicine · 2000
- The melanocortin system in control of inflammationThe Scientific World JOURNAL · 2010
- Targeting melanocortin receptors as potential novel therapeuticsPharmacology & Therapeutics · 2006
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