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Inhalation Toxicology
International Forum for Respiratory Research
Volume 22, 2010 - Issue 7
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Research Article

Carbon dioxide is largely responsible for the acute inflammatory effects of tobacco smoke

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Pages 543-551 | Received 04 Nov 2009, Accepted 14 Dec 2009, Published online: 13 Apr 2010
 

Abstract

Tobacco smoking is responsible for a vast array of diseases, particularly chronic bronchitis and lung cancer. It is still unclear which constituent(s) of the smoke is responsible for its toxicity. The authors decided to focus on carbon dioxide, since its level of concentration in mainstream cigarette smoke is about 200 times higher than in the atmosphere. The authors previously demonstrated that inhalation of carbon dioxide concentrations above 5% has a deleterious effect on lungs. In this study, the authors assessed the inflammatory potential of carbon dioxide contained in cigarette smoke. Mice were exposed to cigarette smoke containing a high or reduced CO2 level by filtration through a potassium hydroxyde solution. The inflammatory response was evaluated by histological analysis, protein phosphatase 2 A (PP2A) and nuclear factor (NF)-κB activation, and proinflammatory cytokine secretion measurements. The data show that the toxicity of cigarette smoke may be largely due to its high level of CO2. Pulmonary injuries consequent to tobacco smoke inhalation observed by histology were greatly diminished when CO2 was removed. Cigarette smoke exposure causes an inflammatory response characterized by PP2A and NF-κB activation followed by proinflammatory cytokine secretion. This inflammatory response was reduced when the cigarette smoke was filtered through a potassium hydroxide column, and reestablished when CO2 was injected downstream from the filtration column.Given that there is an extensive literature linking a chronic inflammatory response to the major smoking-related diseases, these data suggest that carbon dioxide may play a key role in the causation of these diseases by tobacco smoking.

Acknowledgments

We wish to acknowledge the help of Edward Sanders and Jean-Marc Steyaert.

Declaration of interest

This work was funded by Biorébus company. Biorébus company is applying for a patent relating to the content of this paper. The other authors declare that they have no competing interest.

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