TY - JOUR
T1 - Inhibition of systemic inflammation by central action of the neuropeptide α-melanocyte-stimulating hormone
AU - Hernàndez, René Delgado
AU - Demitri, Maria Teresa
AU - Carlin, Andrea
AU - Meazza, Cristina
AU - Villa, Pia
AU - Ghezzi, Pietro
AU - Lipton, James M.
AU - Catania, Anna
PY - 1999/4
Y1 - 1999/4
N2 - The neuropeptide α-melanocyte stimulating hormone (α-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central α-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-α and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of α-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central α-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 α-MSH. Intraperitoneal administration of the small dose of α-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central α-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 α-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by α-MSH could be used to treat systemic inflammation.
AB - The neuropeptide α-melanocyte stimulating hormone (α-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central α-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-α and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of α-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central α-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 α-MSH. Intraperitoneal administration of the small dose of α-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central α-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 α-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by α-MSH could be used to treat systemic inflammation.
KW - α-Melanocyte stimulating hormone
KW - Endotoxin
KW - Nitric oxide
KW - Systemic inflammation
KW - Tumor necrosis factor-α
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UR - http://www.scopus.com/inward/citedby.url?scp=2442742399&partnerID=8YFLogxK
M3 - Article
C2 - 10213917
AN - SCOPUS:2442742399
VL - 6
SP - 187
EP - 192
JO - NeuroImmunoModulation
JF - NeuroImmunoModulation
SN - 1021-7401
IS - 3
ER -