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Published ahead of print on August 18, 2004, doi:10.1164/rccm.200311-1521OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 11, December 2004, 1164-1171

A more recent version of this article appeared on December 1, 2004
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Submitted on November 10, 2003
Accepted on August 12, 2004

Impact of Cigarette Smoke on Clearance and Inflammation following Pseudomonas aeruginosa Infection

Anna G Drannik1, Mahmoud A Pouladi1, Clinton S Robbins1, Susanna I Goncharova1, Sussan Kianpour1, and Martin R Stampfli1*

1 Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada

* To whom correspondence should be addressed. E-mail: stampfli{at}mcmaster.ca.

The objective of this study was to investigate the impact of cigarette smoke on bacterial clearance and immune inflammatory parameters following infection with Pseudomonas aeruginosa in mice. We observed a delayed rate of bacterial clearance in smoke exposed, compared to sham exposed, mice. This was associated with increased inflammation characterized by greater numbers of neutrophils and mononuclear cells in the bronchoalveolar lavage. Following infection, we observed increased levels of pro-inflammatory cytokines (TNF{alpha}, IL-1{beta} and IL-6) and chemokines (MCP-1 and MIP-2) as well as myeloperoxidase and proteolytic activity in the lungs of smoke exposed, compared to sham exposed, animals. Delayed clearance was associated with increased morbidity and greater weight loss of smoke exposed mice. Following delivery of inactivated bacteria, we observed a similar inflammatory response, clinical score, and TNF{alpha} expression in smoke and sham exposed animals suggesting that increased inflammation and altered clinical presentation are due to the delayed rate of bacterial clearance. Our findings suggest that cigarette smoke affects respiratory immune-inflammatory responses elicited by bacteria. We postulate that altered respiratory host defense may be implicated in smoking-related diseases such as COPD.
Key words: Tobacco, COPD, bacterial infection, mice




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