Tobacco Smoke Exposure and Altered Nasal Responses to Live Attenuated Influenza Virus.

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Abstract
Background:
Epidemiologic evidence links tobacco smoke and increased risk for influenza in humans, but the specific host defense pathways involved are unclear.

Objective. Develop a model to examine influenza-induced innate immune responses in humans and test the hypothesis that cigarette smoke exposure alters nasal inflammatory and antiviral responses to live attenuated influenza virus (LAIV).

Methods.
This was an observational cohort study comparing nasal mucosal responses to LAIV among young adult active smokers (n=17), nonsmokers exposed to secondhand smoke (SHS, n=20), and unexposed controls (n=23). Virus RNA and inflammatory factors were measured in nasal lavage fluids (NLF) serially after LAIV inoculation. For key endpoints, peak and total (area under curve) responses were compared among groups. Results. Compared with controls, NLF IL-6 responses to LAIV (peak and total) were suppressed in smokers. Virus RNA in NLF cells was significantly increased in smokers, as were IP-10/virus ratios. Responses in SHS exposed subjects were generally intermediate between controls and smokers. There were significant associations between urine cotinine and NLF IL-6 responses (negative correlation) or virus RNA in NLF cells (positive correlation) for all subjects combined.

Conclusions.
Nasal inoculation with LAIV results in measurable inflammatory and antiviral responses in human volunteers, thus providing a model for investigating environmental effects on influenza infections in humans. Exposure to cigarette smoke was associated with suppression of specific nasal inflammatory and antiviral responses, as well as increased virus quantity, after nasal inoculation with LAIV. These data suggest mechanisms for increased susceptibility to influenza infection among persons exposed to tobacco smoke.

Noah TL, Zhou H, Monaco J, Horvath K, Herbst M, Jaspers I.
University of North Carolina.

http://www.ncbi.nlm.nih.gov/pubmed/20920950

 

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Re: Tobacco Smoke Exposure and Altered Nasal Responses to Live Attenuated Influenza Virus.

Nasal lavage natural killer cell function is suppressed in smokers after live attenuated influenza virus

Katherine M Horvath, Margaret Herbst, Haibo Zhou, Hongtao Zhang, Terry L Noah and Ilona Jaspers

Respiratory Research 2011, 12:102 doi:10.1186/1465-9921-12-102
Published: 4 August 2011

Background
Modified function of immune cells in nasal secretions may play a role in the enhanced susceptibility to respiratory viruses that is seen in smokers. Innate immune cells in nasal secretions have largely been characterized by cellular differentials using morphologic criteria alone, which have successfully identified neutrophils as a significant cell population within nasal lavage fluid (NLF) cells. However, flow cytometry may be a superior method to fully characterize NLF immune cells. We therefore characterized immune cells in NLF by flow cytometry, determined the effects of live attenuated influenza virus (LAIV) on NLF and peripheral blood immune cells, and compared responses in samples obtained from smokers and nonsmokers.

Methods
In a prospective observational study, we characterized immune cells in NLF of nonsmokers at baseline using flow cytometry and immunohistochemistry. Nonsmokers and smokers were inoculated with LAIV on day 0 and serial nasal lavages were collected on days 1-4 and day 9 post-LAIV. LAIV-induced changes of NLF cells were characterized using flow cytometry. Cell-free NLF was analyzed for immune mediators by bioassay. Peripheral blood natural killer (NK) cells from nonsmokers and smokers at baseline were stimulated in vitro with LAIV followed by flow cytometric and mediator analyses.

Results
CD45(+)CD56(-)CD16(+) neutrophils and CD45(+)CD56(+) NK cells comprised median 4.62% (range 0.33-14.52) and 23.27% (18.29-33.97), respectively, of non-squamous NLF cells in nonsmokers at baseline. LAIV did not induce changes in total NK cell or neutrophil percentages in either nonsmokers or smokers. Following LAIV inoculation, CD16(+) NK cell percentages and granzyme B levels increased in nonsmokers, and these effects were suppressed in smokers. LAIV inoculation enhanced expression of activating receptor NKG2D and chemokine receptor CXCR3 on peripheral blood NK cells from both nonsmokers and smokers in vitro but did not induce changes in CD16(+) NK cells or granzyme B activity in either group.

Conclusions
These data are the first to identify NK cells as a major immune cell type in the NLF cell population and demonstrate that mucosal NK cell cytotoxic function is suppressed in smokers following LAIV. Altered NK cell function in smokers suggests a potential mechanism that may enhance susceptibility to respiratory viruses.

http://respiratory-research.com/content/12/1/102/abstract