Journal
SHOCK
Volume 24, Issue 6, Pages 583-589Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.shk.0000185795.96964.71
Keywords
inflammation; NF-kappa B; MAPK; rat; cecal ligation and puncture; signal transduction
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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 anti inflammatory effects of GLN in the lung. Either 0.75 g/kg of GLN or saline placebo (SP) was administered to male rats 1 In after cecal ligation and puncture (CLP). NF-kappa B activation, lKB alpha degradation, phosphorylation of p38 MAPK, ERK, and MKP-1 expression were evaluated in lung tissue 6 h post-CLP. Lung tissue iNOS and eNOS, TNF-alpha, IL-6, and IL-18 cytokines were assayed. Last, lung histopathology for occurrence of ARDS and survival were examined. GLN given 1 h postsepsis led to inhibition of lung tissue NF-kappa B activation (P < 0.001 vs. SP), attenuated degradation of lKBa, and inhibited phosphorylation of p38 MAPK, and ERK, pathways critical for cytokine release. GLN treatment increased MKP-1 peptide expression and significantly attenuated TNF-alpha and IL-6 6 h after CLP. IL-18 was attenuated by GLN at multiple time points post-CLP. Further, GLN abrogated increases in lung NOS expression and enhanced lung eNOS postsepsis. Finally, GLN prevented the histopathologic appearance of ARDS after sepsis and significantly improved survival. 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-kappa B, p38 MAPK, ERK, and MKP-1. GLN also showed an inhibition of increases in NOS expression. The antiinflammatory effect of GLN was associated with attenuation of ARDS and mortality.
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