TY - JOUR
T1 - α-MSH in systemic inflammation. Central and peripheral actions
AU - Catania, Anna
AU - Delgado, René
AU - Airaghi, Lorena
AU - Cutuli, Mariagrazia
AU - Garofalo, Letizia
AU - Carlin, Andrea
AU - Demitri, Maria Teresa
AU - Lipton, James M.
PY - 1999
Y1 - 1999
N2 - Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on α-melanocyte stimulating hormone (α-MSH). Increases in circulating TNF-α and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, 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. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central α-MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central α-MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by α-MSH could be used to treat systemic inflammation. In addition to its central influences, α-MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. α-MSH reduces chemotaxis of human neutrophils and production of TNF-α, neopterin, and NO by monocytes. In research on septic patients, α-MSH inhibited release of TNF-α, interleukin-1β (IL-1β), and interleukin-8 (IL-8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.
AB - Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on α-melanocyte stimulating hormone (α-MSH). Increases in circulating TNF-α and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, 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. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central α-MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central α-MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by α-MSH could be used to treat systemic inflammation. In addition to its central influences, α-MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. α-MSH reduces chemotaxis of human neutrophils and production of TNF-α, neopterin, and NO by monocytes. In research on septic patients, α-MSH inhibited release of TNF-α, interleukin-1β (IL-1β), and interleukin-8 (IL-8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.
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M3 - Article
C2 - 10816651
AN - SCOPUS:0032786477
VL - 885
SP - 183
EP - 187
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
SN - 0077-8923
ER -