HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/1/G9    most recent 90243.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Scott, J. R. Articles by Potter, R. F. Search for Related Content PubMed PubMed Citation Articles by Scott, J. R. Articles by Potter, R. F.

INFLAMMATION/IMMUNITY/MEDIATORS

Low-dose inhaled carbon monoxide attenuates the remote intestinal inflammatory response elicited by hindlimb ischemia-reperfusion

¹Medical Biophysics, ²Surgery, and ³Critical Care, University of Western Ontario; ⁴The Centre for Critical Illness Research, and Lawson Health Research Institute, London, Ontario, Canada; ⁵Immunobiology Research Center, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Submitted 18 March 2008 ; accepted in final form 7 October 2008

Heme oxygenase (HO) represents the rate-limiting enzyme in the degradation of heme into carbon monoxide (CO), iron, and biliverdin. Recent evidence suggests that several of the beneficial properties of HO, may be linked to CO. The objectives of this study were to determine if low-dose inhaled CO reduces remote intestinal leukocyte recruitment, proinflammatory cytokine expression, and oxidative stress elicited by hindlimb ischemia-reperfusion (I/R). Male mice underwent 1 h of hindlimb ischemia, followed by 3 h of reperfusion. Throughout reperfusion, mice were exposed to AIR or AIR + CO (250 ppm). Following reperfusion, the distal ileum was exteriorized to assess the intestinal inflammatory response by quantifying leukocyte rolling and adhesion in submucosal postcapillary venules with the use of intravital microscopy. Ileum samples were also analyzed for proinflammatory cytokine expression [tumor necrosis factor (TNF)- and interleukin (IL)-1β] and malondialdehyde (MDA) with the use of enzyme-linked immunosorbent assay and thiobarbituric acid reactive substances assays, respectively. I/R + AIR led to a significant decrease in leukocyte rolling velocity and a sevenfold increase in leukocyte adhesion. This was also accompanied by a significant 1.3-fold increase in ileum MDA and 2.3-fold increase in TNF- expression. Treatment with AIR + CO led to a significant reduction in leukocyte recruitment and TNF- expression elicited by I/R; however, MDA levels remained unchanged. Our data suggest that low-dose inhaled CO selectively attenuates the remote intestinal inflammatory response elicited by hindlimb I/R, yet does not provide protection against intestinal lipid peroxidation. CO may represent a novel anti-inflammatory therapeutic treatment to target remote organs following acute trauma and/or I/R injury.

carbon monoxide; inflammation; ischemia-reperfusion; systemic inflammatory response syndrome