Efficacy and safety of inhaled carbon monoxide during pulmonary inflammation in mice.

PloS One
Michael R WilsonMasao Takata

Abstract

Pulmonary inflammation is a major contributor to morbidity in a variety of respiratory disorders, but treatment options are limited. Here we investigate the efficacy, safety and mechanism of action of low dose inhaled carbon monoxide (CO) using a mouse model of lipopolysaccharide (LPS)-induced pulmonary inflammation. Mice were exposed to 0-500 ppm inhaled CO for periods of up to 24 hours prior to and following intratracheal instillation of 10 ng LPS. Animals were sacrificed and assessed for intraalveolar neutrophil influx and cytokine levels, flow cytometric determination of neutrophil number and activation in blood, lung and lavage fluid samples, or neutrophil mobilisation from bone marrow. When administered for 24 hours both before and after LPS, inhaled CO of 100 ppm or more reduced intraalveolar neutrophil infiltration by 40-50%, although doses above 100 ppm were associated with either high carboxyhemoglobin, weight loss or reduced physical activity. This anti-inflammatory effect of CO did not require pre-exposure before induction of injury. 100 ppm CO exposure attenuated neutrophil sequestration within the pulmonary vasculature as well as LPS-induced neutrophilia at 6 hours after LPS, likely due to abrogation of neutrophil...Continue Reading

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Citations

Apr 23, 2011·Journal of Applied Physiology·Anthony D DorrMasao Takata
Oct 19, 2011·The European Respiratory Journal·Brijesh V PatelMasao Takata
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Dec 19, 2020·Intensive Care Medicine Experimental·Laura ChimentiAntonio Artigas
Apr 11, 2021·Nitric Oxide : Biology and Chemistry·Christopher P HopperJakob Wollborn

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Methods Mentioned

BETA
lavage
ELISA
flow cytometry
flow

Software Mentioned

GraphPad Prism

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