Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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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. ⋯ The protective effect of CGRP correlates with an inhibition of TNF-alpha and an induction of IL-6 and IL-10 in mice sera 90 min after LPS challenge. Finally, CGRP significantly inhibits LPS-induced TNF-alpha 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.
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Glutamine (GLN) has been shown to attenuate cytokine release from LPS-stimulated human peripheral blood mononuclear cells; however, the in vivo antiinflammatory effect of GLN in polymicrobial sepsis and ARDS is unknown. This study evaluates the effect of GLN on inflammatory cytokine release and the pathways that may mediate antiinflammatory effects of GLN in the lung. Either 0.75 g/kg of GLN or saline placebo (SP) was administered to male rats 1 h after cecal ligation and puncture (CLP). ⋯ These data reveal that GLN exerts an antiinflammatory effect in sepsis that may be mediated via attenuation of multiple pathways of inflammation such as NF-kappaB, p38 MAPK, ERK, and MKP-1. GLN also showed an inhibition of increases in iNOS expression. The antiinflammatory effect of GLN was associated with attenuation of ARDS and mortality.