Influenza virus-induced lung inflammation was modulated by cigarette smoke exposure in mice.
Although smokers have increased susceptibility and severity of seasonal influenza virus infection, there is no report about the risk of 2009 pandemic H1N1 (pdmH1N1) or avian H9N2 (H9N2/G1) virus infection in smokers. In our study, we used mouse model to investigate the effect of cigarette smoke on pdmH1N1 or H9N2 virus infection. Mice were exposed to cigarette smoke for 21 days and then infected with pdmH1N1 or H9N2 virus. Control mice were exposed to air in parallel. We found that cigarette smoke exposure alone significantly upregulated the lung inflammation. Such prior cigarette smoke exposure significantly reduced the disease severity of subsequent pdmH1N1 or H9N2 virus infection. For pdmH1N1 infection, cigarette smoke exposed mice had significantly lower mortality than the control mice, possibly due to the significantly decreased production of inflammatory cytokines and chemokines. Similarly, after H9N2 infection, cigarette smoke exposed mice displayed significantly less weight loss, which might be attributed to lower cytokines and chemokines production, less macrophages, neutrophils, CD4+ and CD8+ T cells infiltration and reduced lung damage compared to the control mice. To further investigate the underlying mechanism, we used nicotine to mimic the effect of cigarette smoke both in vitro and in vivo. Pre-treating the primary human macrophages with nicotine for 72 h significantly decreased their expression of cytokines and chemokines after pdmH1N1 or H9N2 infection. The mice subcutaneously and continuously treated with nicotine displayed significantly less weight loss and lower inflammatory response than the control mice upon pdmH1N1 or H9N2 infection. Moreover, α7 nicotinic acetylcholine receptor knockout mice had more body weight loss than wild-type mice after cigarette smoke exposure and H9N2 infection. Our study provided the first evidence that the pathogenicity of both pdmH1N1 and H9N2 viruses was alleviated in cigarette smoke exposed mice, which might partially be attributed to the immunosuppressive effect of nicotine.
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Yan
Y
Han
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Man To
MT
Ling
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Huawei
H
Mao
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Jian
J
Zheng
State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical College, Guangzhou, People's Republic of China.
Ming
M
Liu
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Kwok Tai
KT
Lam
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Yuan
Y
Liu
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Wenwei
W
Tu
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.
Yu-Lung
YL
Lau
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D003367:Cotinine / Q000097:blood; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053127:Influenza A Virus, H9N2 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000150:complications* / Q000821:virology*; D011014:Pneumonia / Q000097:blood / Q000150:complications* / Q000821:virology*; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects* / Q000097:blood; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000172:deficiency / Q000378:metabolism
D018925:Chemokines; C579166:Chrna7 protein, mouse; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D003367:Cotinine