Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9987
Title: Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia
Authors: Gomes, Rachel Novaes
Faria Neto, Hugo Caire de Castro
Bozza, Patrícia Torres
Soares, Milena Botelho Pereira
Shoemaker, Charles B.
David, John R.
Bozza, Marcelo Torres
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
University School of Veterinary Medicine. Division of Infectious Diseases. Department of Biomedical Sciences. North Grafton, Massachusettes, USA.
Harvard School of Public Health. Department of Tropical Public Health. Boston, Massachusettes, USA.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Laboratório de Inflamação e Imunidade. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.
Abstract: ABSTRACT: Calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide present in central and peripheral neurons, is released at inflammatory sites and inhibits several macrophage, dendritic cell, and lymphocyte functions. In the present study, we investigated the role of CGRP in models of local and systemic acute inflammation and on macrophage activation induced by lipopolysaccharide (LPS). Intraperitoneal pretreatment with synthetic CGRP reduces in approximately 50% the number of neutrophils in the blood and into the peritoneal cavity 4 h after LPS injection. CGRP failed to inhibit neutrophil recruitment induced by the direct chemoattractant platelet-activating factor, whereas it significantly inhibited LPSinduced KC generation, suggesting that the effect of CGRP on neutrophil recruitment is indirect, acting on chemokine production by resident cells. Pretreatment of mice with 1 mg of CGRP protects against a lethal dose of LPS. The CGRPinduced protection is receptor mediated because it is completely reverted by the CGRP receptor antagonist, CGRP 8-37. The protective effect of CGRP correlates with an inhibition of TNF-a and an induction of IL-6 and IL-10 in mice sera 90 min after LPS challenge. Finally, CGRP significantly inhibits LPS-induced TNF-a released from mouse peritoneal macrophages. These results suggest that activation of the CGRP receptor on macrophages during acute inflammation could be part of the negative feedback mechanism controlling the extension of acute inflammatory responses.
Keywords: LPS
CGRP
Cytokines
Inflammation
Endotoxemia
Issue Date: 2005
Publisher: Lippincott Williams & Wilkins
Citation: GOMES, R. N. et al. Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia. Shock, v. 24, n. 6, p. 590-59, 2005.
DOI: 10.1097/01.shk.0000183395.29014.7c
ISSN: 1073-2322
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos
BA - IGM - Artigos de Periódicos

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