Melanocortin modulation of inflammatory cytokine and neuroendocrine responses to endotoxin in the monkey.

Details

Serval ID
serval:BIB_636F642D4DC4
Type
Article: article from journal or magazin.
Collection
Publications
Title
Melanocortin modulation of inflammatory cytokine and neuroendocrine responses to endotoxin in the monkey.
Journal
Endocrinology
Author(s)
Vulliémoz N.R., Xiao E., Xia-Zhang L., Ferin M., Wardlaw S.L.
ISSN
0013-7227 (Print)
ISSN-L
0013-7227
Publication state
Published
Issued date
04/2006
Peer-reviewed
Oui
Volume
147
Number
4
Pages
1878-1883
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Abstract
alpha-MSH has potent antiinflammatory properties, but little is known about the specific melanocortin receptors (MC-Rs) that mediate these effects or about the role of the melanocortin system in modulating cytokine responses to an inflammatory challenge in the primate in vivo. We, therefore, studied the effects of infusion of the alpha-MSH agonist, [Nle(4),d-Phe(7)]-alpha-MSH (NDP-MSH); the alpha-MSH antagonist, SHU9119; and the selective MC3-R agonist, D-Trp8-gamma-MSH, compared with saline, on proinflammatory cytokine (TNF-alpha, IL-1beta, and IL-6), antiinflammatory cytokine [IL-10 and IL-1 receptor antagonist (IL-1ra)], and pituitary-adrenal responses to endotoxin in ovariectomized monkeys. In the first study NDP-MSH or SHU9119 was infused iv for 7 h starting at 0800 h, endotoxin was injected at 1000 h, and serial blood samples were collected (n = 6). NDP-MSH significantly attenuated proinflammatory cytokine responses to endotoxin. The area under the response curve (AUC) decreased by 61% for TNF-alpha (P = 0.02), 47% for IL-1beta (P = 0.02), and 41% for IL-6 (P = 0.04); there was no effect on IL-1ra or IL-10. SHU9119 did not affect proinflammatory cytokine responses, but decreased the IL-10 response by 31% (P = 0.03). NDP-MSH also attenuated ACTH (P < 0.001) and cortisol (P = 0.02) responses. In a second study, the effects of d-Trp8-gamma-MSH were similarly examined in seven monkeys. The AUC for IL-6 was decreased by 37% (P = 0.04) by d-Trp8-gamma-MSH; the AUC for IL-10 was increased by 22%, but this was not significant. However, the ratio of IL-6 to IL-10 was significantly decreased by d-Trp8-gamma-MSH (P = 0.04), consistent with a relatively more antiinflammatory cytokine environment. These results indicate that NDP-MSH can attenuate proinflammatory cytokine responses in the primate, consistent with previous studies in the rodent, and provide new evidence for a role for MC3-R in this process. Moreover, they show for the first time that SHU9119, a mixed MC3/4-R antagonist, can decrease the IL-10 response, establishing a physiological role for endogenous MSH in modulating the release of an antiinflammatory cytokine.
Keywords
Adrenocorticotropic Hormone/blood, Animals, Cytokines/biosynthesis, Female, Hydrocortisone/blood, Hypothalamo-Hypophyseal System/drug effects, Lipopolysaccharides/pharmacology, Macaca mulatta, Melanocyte-Stimulating Hormones/pharmacology, Pituitary-Adrenal System/drug effects, Receptors, Melanocortin/physiology, alpha-MSH/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
02/10/2019 19:37
Last modification date
08/10/2019 5:26
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