NDP-MSH inhibits neutrophil migration through nicotinic and adrenergic receptors in experimental peritonitis.

Journal Article (Journal Article)

Melanocortin is a potent anti-inflammatory molecule. However, little is known about the effect of melanocortin on acute inflammatory processes such as neutrophil migration. In the present study, we investigated the ability of [Nle4, D-Phe7]-melanocyte-stimulating hormone (NDP-MSH), a semisynthetic melanocortin compound, in the inhibition of neutrophil migration in carrageenin-induced peritonitis model. Herein, subcutaneous pretreatment with NDP-MSH decreased neutrophil trafficking in the peritoneal cavity in a dose-dependent manner. NDP-MSH inhibited vascular leakage, leukocyte rolling, and adhesion and reduced peritoneal macrophage inflammatory protein 2, but not TNF-alpha, IL-1beta, IL-10, and keratinocyte-derived chemokine production. In addition, the effect on neutrophil migration was reverted by the pretreatment with both propranolol (a nonselective beta-adrenergic antagonist) and mecamylamine (a nonselective nicotinic antagonist) but not by splenectomy surgery. Moreover, NDP-MSH intracerebroventricular administration inhibited neutrophil migration, indicating participation of the central nervous system. Our results propose that the NDP-MSH effect may be due to a spleen-independent neuro-immune pathway that efficiently regulates excessive neutrophil recruitment to tissues.

Full Text

Duke Authors

Cited Authors

  • Figueiredo, J; Ferreira, AE; Silva, RL; Ulloa, L; Grieco, P; Cunha, TM; Ferreira, SH; Cunha, FDQ; Kanashiro, A

Published Date

  • April 2013

Published In

Volume / Issue

  • 386 / 4

Start / End Page

  • 311 - 318

PubMed ID

  • 23338711

Electronic International Standard Serial Number (EISSN)

  • 1432-1912

Digital Object Identifier (DOI)

  • 10.1007/s00210-013-0834-7


  • eng

Conference Location

  • Germany