Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice

Rationale: Studies have shown that cigarette smoke impacts respira-tory 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 re-sponses 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 2.5 103 pfu (low dose) or 2.5 105 pfu (high dose) influenza virus. Measurements and Main Results: Although smoke exposure attenu-ated the airway’s inflammatory response to low-dose infection, we observed increased inflammation in smoke-exposed comparedwith sham-exposed mice after infection with high-dose influenza, de-spite a similar rate of viral clearance. The heightened inflammatory response was associated with increased expression of tumor necro-sis factor-, interleukin-6, and type 1 IFN in the airway, and in-creased 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, inmice, cigarette smoke affects primary antiviral immune-inflammatory responses, whereas sec-ondary immune protection remains intact