α-MSH peptides inhibit acute inflammation induced in mice by rIL-1β, rIL-6, rTNF-α and endogenous pyrogen but not that caused by LTB4, PAF and rIL-8

Melanie E. Hiltz, Anna Catania, James M. Lipton

Research output: Contribution to journalArticle

Abstract

The neuropeptide α-melanocyte stimulating hormone [α-MSH(1-13)] occurs in the pituitary, brain, skin and other tissues and receptors for this molecule are likewise widespread. In previous research, this tridecapeptide, which shares its amino acid sequence with ACTH(1-13), was shown to have both potent antipyretic activity and a role in the endogenous control of the febrile response. α-MSH(1-13) and its COOH-terminal tripeptide were subsequently found to inhibit inflammation induced by general stimuli such as topical application of an irritant. The aim in the present experiments was to determine if these peptides can inhibit acute inflammatory responses induced in mice by injection of individual cytokines, endogenous pyrogen (EP), a natural cytokine mixture, and other mediators of inflammation. Inflammation induced in the mouse ear by rIL-1β, rIL-6 or rTNF-α was inhibited by α-MSH and a d-valine-substituted analog of α-MSH(11-13) whereas substantial doses of α-MSH(1-13) did not alter inflammation induced by LTB4, PAF and IL-8. Both peptides inhibited edema caused in the mouse paw by local injection of EP. The results indicate that α-MSH molecules antagonize the actions of certain cytokine mediators of inflammation, consistent with previous observations of anti-cytokine activity of these peptides. Failure to inhibit edema caused by LTB4, PAF and IL-8 suggests that, in inflammation induced by general stimuli, such as EP, the peptides act prior to the release of these mediators of the inflammatory response. Because of the anticytokine/anti-inflammatory actions of the α-MSH molecules they may be useful in understanding the cytokine network and for treatment of inflammatory diseases.

Original languageEnglish
Pages (from-to)320-328
Number of pages9
JournalCytokine
Volume4
Issue number4
DOIs
Publication statusPublished - 1992

Keywords

  • anti-inflammatory peptides
  • cytokines
  • host response
  • inflammation mediators
  • α-MSH

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

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