title: Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens.
abstract: 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 C(4); 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.
authors.affiliation: Immunology Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
authors.forename: Neerad C
authors.initials: NC
authors.lastname: Mishra
authors.forename: Jules
authors.initials: J
authors.lastname: Rir-Sima-Ah
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Langley
authors.forename: Shashi P
authors.initials: SP
authors.lastname: Singh
authors.forename: Juan C
authors.initials: JC
authors.lastname: Peña-Philippides
authors.forename: Takeshi
authors.initials: T
authors.lastname: Koga
authors.forename: Seddigheh
authors.initials: S
authors.lastname: Razani-Boroujerdi
authors.forename: Julie
authors.initials: J
authors.lastname: Hutt
authors.forename: Matthew
authors.initials: M
authors.lastname: Campen
authors.forename: K Chul
authors.initials: KC
authors.lastname: Kim
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.forename: Mohan L
authors.initials: ML
authors.lastname: Sopori
mesh_terms: D000485:Allergens / Q000276:immunology*; D031164:Ambrosia / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D020397:Goblet Cells / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D017997:Leukotriene C4 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D032342:Muscle Cells / Q000276:immunology* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; C524678:MUC5AC protein, human; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D017997:Leukotriene C4; D007073:Immunoglobulin E; D009538:Nicotine