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Immunology Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108
Allergic asthma, an inflammatory disease characterized by the infiltration and activation of various leukocytes, the production of Th2 cytokines and leukotrienes, and atopy, also affects the function of other cell types, causing goblet cell hyperplasia/hypertrophy, increased mucus production/secretion, and airway hyperreactivity. Eosinophilic inflammation is a characteristic feature of human asthma, and recent evidence suggests that eosinophils also play a critical role in T cell trafficking in animal models of asthma. Nicotine is an anti-inflammatory, but the association between smoking and asthma is highly contentious and some report that smoking cessation increases the risk of asthma in ex-smokers. To ascertain the effects of nicotine on allergy/asthma, Brown Norway rats were treated with nicotine and sensitized and challenged with allergens. The results unequivocally show that, even after multiple allergen sensitizations, nicotine dramatically suppresses inflammatory/allergic parameters in the lung including the following: eosinophilic/lymphocytic emigration; mRNA and/or protein expression of the Th2 cytokines/chemokines IL-4, IL-5, IL-13, IL-25, and eotaxin; leukotriene C4; and total as well as allergen-specific IgE. Although nicotine did not significantly affect hexosaminidase release, IgG, or methacholine-induced airway resistance, it significantly decreased mucus content in bronchoalveolar lavage; interestingly, however, despite the strong suppression of IL-4/IL-13, nicotine significantly increased the intraepithelial-stored mucosubstances and Muc5ac mRNA expression. These results suggest that nicotine modulates allergy/asthma primarily by suppressing eosinophil trafficking and suppressing Th2 cytokine/chemokine responses without reducing goblet cell metaplasia or mucous production and may explain the lower risk of allergic diseases in smokers. To our knowledge this is the first direct evidence that nicotine modulates allergic responses.
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1 This work was supported in part by grants from the National Institutes of Health (R01-DA017003, R01-DA04208-15, and R01-DA042087S).
2 Address correspondence and reprint requests to Dr. Mohan L. Sopori, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive Southeast, Albuquerque, NM 87108. E-mail address: msopori{at}lrri.org
3 Abbreviations used in this paper: AHR, airway hyperresponsiveness; AB-PAS, Alcian Blue and periodic acid-Schiff solution; BAL, bronchoalveolar lavage; BALF, bronchoalveolar lavage fluid; BN, Brown Norway; Ct, threshold cycle; CON, control; GABA, 
-aminobutyric acid; HDM, house dust mite; IHC, immunohistochemistry; i.t., intratracheal(ly); LTC4, leukotriene C4; NRW, NT treated and RW sensitized/challenged; NT, nicotine; qPCR, real-time quantitative PCR; RW, ragweed.
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  S. P. Singh, N. C. Mishra, J. Rir-sima-ah, M. Campen, V. Kurup, S. Razani-Boroujerdi, and M. L. Sopori Maternal Exposure to Secondhand Cigarette Smoke Primes the Lung for Induction of Phosphodiesterase-4D5 Isozyme and Exacerbated Th2 Responses: Rolipram Attenuates the Airway Hyperreactivity and Muscarinic Receptor Expression but Not Lung Inflammation and Atopy J. Immunol., August 1, 2009; 183(3): 2115 - 2121. [Abstract] [Full Text] [PDF]
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