Article
Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia
Registro en:
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.
1073-2322
10.1097/01.shk.0000183395.29014.7c
Autor
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
Resumen
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.