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Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice

Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, Department of Biology, and Department of Medicine, McMaster University, Hamilton; and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada

Correspondence and requests for reprints should be addressed to Martin R. Stämpfli, Ph.D., McMaster University, Department of Pathology and Molecular Medicine, MDCL, Room 4011, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada. E-mail: stampfli{at}mcmaster.ca

Rationale: Studies have shown that cigarette smoke impacts respiratory host defense mechanisms; however, it is poorly understood how these smoke-induced changes impact the overall ability of the host to deal with pathogenic agents.

Objective: The objective of this study was to investigate the impact of mainstream cigarette smoke exposure on immune inflammatory responses and viral burden after respiratory infection with influenza A.

Methods: C57BL/6 mice were sham- or smoke-exposed for 3 to 5 mo and infected with either 2.5 x 10³ pfu (low dose) or 2.5 x 10⁵ pfu (high dose) influenza virus.

Measurements and Main Results: Although smoke exposure attenuated the airway's inflammatory response to low-dose infection, we observed increased inflammation in smoke-exposed compared with sham-exposed mice after infection with high-dose influenza, despite a similar rate of viral clearance. The heightened inflammatory response was associated with increased expression of tumor necrosis factor-, interleukin-6, and type 1 IFN in the airway, and increased mortality. Importantly, smoke exposure did not interfere with the development of influenza-specific memory responses; sham- and smoke-exposed animals were equally protected upon viral rechallenge.

Conclusion: Our study suggests that, in mice, cigarette smoke affects primary antiviral immune-inflammatory responses, whereas secondary immune protection remains intact.

Key Words: chronic obstructive pulmonary disease • inflammation • immunity • neutrophils

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Epidemiological studies show that smoking is associated with an increased incidence of respiratory tract infections. These findings suggest that cigarette smoking may alter the way respiratory pathogenic microorganisms are handled. What This Study Adds to the Field Cigarette smoke affects primary antiviral responses, yet secondary immune protection remains intact. Exaggerated inflammatory responses to viral agents likely contribute to the decline in clinical status associated with COPD exacerbations.

 

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