Gamma(2)-melanocyte-stimulating hormone suppression of systemic inflammatory responses to endotoxin is associated with modulation of central autonomic and neuroendocrine activities.
Central autonomic and neuroendocrine activities are important components of the host response to bacterial inflammation. We demonstrate that intravenous infusion of gamma(2)-melanocyte-stimulating hormone (gamma(2)-MSH), a potent autonomic regulating peptide, prevents lipopolysaccharide (LPS)-induced hypotension and tachycardia, and modulates the ACTH response to endotoxin. In the hypothalamic paraventricular nucleus, a major neuroendocrine and autonomic center, gamma(2)-MSH inhibits LPS-induced increases in CRF mRNA levels, but does not suppress LPS-augmented arginine vasopressin heteronuclear RNA expression. In the locus coeruleus, a brainstem noradrenergic center, gamma(2)-MSH inhibits LPS-induced increases in tyrosine hydroxylase mRNA levels. Gamma(2)-MSH inhibits LPS-induced IL-1beta gene expression in the brain, pituitary and thymus, and prevents increases in plasma NO levels. These findings reveal that gamma(2)-MSH attenuates systemic inflammatory responses to endotoxin and suggest that modulation of central autonomic and neuroendocrine activities by gamma(2)-MSH contributes to its anti-inflammatory effects.
Xia
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Department of Cell Biology, Faculty of Medicine and Dentistry, and Center for Neuroscience, University of Alberta, Edmonton, AB, Canada T6G 2H7.
Wikberg
J E
JE
Krukoff
T L
TL
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013610:Tachycardia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism; D019825:gamma-MSH / Q000494:pharmacology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019825:gamma-MSH; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase