Mishra Neerad C, Rir-Sima-Ah Jules, Langley Raymond J, Singh Shashi P, Peña-Philippides Juan C, Koga Takeshi, Razani-Boroujerdi Seddigheh, Hutt Julie, Campen Matthew, Kim K Chul, Tesfaigzi Yohannes, Sopori Mohan L
Immunology Program, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA.
J Immunol. 2008 Jun 1;180(11):7655-63. doi: 10.4049/jimmunol.180.11.7655.
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.
过敏性哮喘是一种炎症性疾病，其特征为多种白细胞浸润和活化、Th2细胞因子和白三烯生成以及特应性，它还会影响其他细胞类型的功能，导致杯状细胞增生/肥大、黏液产生/分泌增加以及气道高反应性。嗜酸性粒细胞炎症是人类哮喘的一个特征，最近的证据表明，在哮喘动物模型中，嗜酸性粒细胞在T细胞迁移中也起着关键作用。尼古丁具有抗炎作用，但吸烟与哮喘之间的关联极具争议，一些报告称戒烟会增加既往吸烟者患哮喘的风险。为了确定尼古丁对过敏/哮喘的影响，对棕色挪威大鼠进行尼古丁处理，并用过敏原进行致敏和激发。结果明确显示，即使经过多次过敏原致敏，尼古丁也能显著抑制肺部的炎症/过敏参数，包括以下各项：嗜酸性粒细胞/淋巴细胞渗出；Th2细胞因子/趋化因子白细胞介素-4、白细胞介素-5、白细胞介素-13、白细胞介素-25和嗜酸性粒细胞趋化因子的mRNA和/或蛋白质表达；白三烯C4；以及总IgE和过敏原特异性IgE。虽然尼古丁对己糖胺酶释放、IgG或乙酰甲胆碱诱导的气道阻力没有显著影响，但它显著降低了支气管肺泡灌洗中的黏液含量；然而，有趣的是，尽管尼古丁强烈抑制白细胞介素-4/白细胞介素-13，但它显著增加了上皮内储存的黏液物质和Muc5ac mRNA表达。这些结果表明，尼古丁主要通过抑制嗜酸性粒细胞迁移和抑制Th2细胞因子/趋化因子反应来调节过敏/哮喘，而不会减少杯状细胞化生或黏液产生，这可能解释了吸烟者患过敏性疾病风险较低的原因。据我们所知，这是尼古丁调节过敏反应的首个直接证据。
