The administration of an alpha-MSH analogue reduces the serum release of IL-1 alpha and TNF alpha induced by the injection of a sublethal dose of lipopolysaccharides in the BALB/c mouse.
The injection of alpha-MSH or of one of its analogues ([Nle4-D.Phe7] alpha-MSH4-10) reduced, in vivo, the release of two cytokines (IL-1 alpha and TNF alpha) involved in inflammation. The inflammatory state was induced in BALB/c mice by intraperitoneal injection of a sublethal dose of lipopolysaccharides (LPS). The assay of these cytokines by ELISA showed a reduction of 20% with alpha-MSH and between 30 and 60% with the alpha-MSH analogue. The alpha-MSH or the analogue was administered in one of two ways: intravenously or subcutaneously. The most efficient method seemed to be the subcutaneous one because it improved the activity 10,000 times more than the intravenous method. Moreover, the analogue induced a regression of mortality in the animals treated by the intravenous method. Our results show that alpha-MSH and one of its analogues inhibit IL-1 alpha and TNF alpha, and can be used as anti-inflammatory molecules.
Institut Européen de Biologie Cellulaire et de Cytopathologie, Ramonville-Saint-Agne, France.
C
C
Gonindard
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C
Goigoux
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Hollande
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LD
D'Hinterland
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH; C024150:MSH, (2-Phe-4-Nle)alpha-