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In mice, cigarette smoke has been reported to have both pro\u2010 and anti\u2010Th2 response effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We hypothesized that combining tobacco cigarette smoke (<jats:styled-content style=\"fixed-case\">tCS<\/jats:styled-content>) with allergen exposure increases inflammation, airway remodelling and lung function in mice. To test this hypothesis, we combined a severe triple allergen model with <jats:styled-content style=\"fixed-case\">tCS<\/jats:styled-content> exposure and investigated whether effects were due to Toll\u2010like receptor 4 signalling and\/or nicotine and also observed when nicotine\u2010free cigarettes were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were sensitized with ovalbumin, cockroach and house dust mite allergen in alum followed by intratracheal challenges with allergen twice a week for 6 weeks or additionally exposed to <jats:styled-content style=\"fixed-case\">tCS<\/jats:styled-content> during the allergen challenge period. Nicotine or nicotine\u2010free herbal cigarette smoke was also applied to allergen challenged mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">tCS<\/jats:styled-content> significantly reduced eosinophil numbers, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105 concentrations in the lung, total and allergen\u2010specific IgE in serum, improved lung function and reduced collagen I levels. With the exception of collagen I all parameters reduced by tobacco cigarette smoke were also reduced in Toll\u2010like receptor 4\u2010deficient mice. Nicotine\u2010free cigarette smoke also had significant anti\u2010inflammatory effects on eosinophils, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105 concentrations in the lung and reduced airway hyperreactivity, albeit weaker than tobacco smoke. Applying nicotine alone also reduced Th2 cytokine levels and eosinophil numbers in the airways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our experiments show that <jats:styled-content style=\"fixed-case\">tCS<\/jats:styled-content> exposure reduces allergen\u2010induced Th2 response in the lung and associated collagen I production and development of airway hyperreactivity. With the exception on collagen I formation, these effects were not dependent on Toll\u2010like receptor 4. The observed anti\u2010Th2 effects of both nicotine and nicotine\u2010free herbal cigarette smoke together suggests that <jats:styled-content style=\"fixed-case\">tCS<\/jats:styled-content> reduces the Th2 responses through nicotine and other products released by burning tobacco.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12665","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T03:46:40Z","timestamp":1445917600000},"page":"957-972","source":"Crossref","is-referenced-by-count":27,"title":["Effects of conventional tobacco smoke and nicotine\u2010free cigarette smoke on airway inflammation, airway remodelling and lung function in a triple allergen model of severe asthma"],"prefix":"10.1111","volume":"46","author":[{"given":"C.","family":"Tilp","sequence":"first","affiliation":[{"name":"Respiratory Diseases Research Boehringer Ingelheim Pharma GmbH &amp; Co. KG Biberach a.d. 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