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 intraveno us infusion of gamma (2)-melanocyte-stimulating hormone (gamma (2)-MSH), a potent autonomic regulating peptide, prevents lipopolysaccharide (LPS)-indu ced hypotension and tachycardia, and modulates the ACTH response to endotox in. 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 heteronuc lear RNA expression. In the locus coeruleus, a brainstem noradrenergic cent er, gamma (2)-MSH inhibits LPS-induced increases in tyrosine hydroxylase mR NA levels. gamma (2)-MSH inhibits LPS-induced IL-1 beta 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 arid suggest that modulation of central autonomic a nd neuroendocrine activities by gamma (2)-MSH contributes to its anti-infla mmatory effects. (C) 2001 Elsevier Science B.V. All rights reserved.