BACKGROUND: Patients with asthma who smoke have reduced lung function, increased exacerbation rates and increased steroid resistance compared to non-smoking asthmatics. In mice, cigarette smoke has been reported to have both pro- and anti-Th2 response effects. OBJECTIVE: We hypothesized that combining tobacco cigarette smoke (tCS) with allergen exposure increases inflammation, airway remodelling and lung function in mice. To test this hypothesis, we combined a severe triple allergen model with tCS exposure and investigated whether effects were due to Toll-like receptor 4 signalling and/or nicotine and also observed when nicotine-free cigarettes were used. METHODS: 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 tCS during the allergen challenge period. Nicotine or nicotine-free herbal cigarette smoke was also applied to allergen challenged mice. RESULTS: tCS significantly reduced eosinophil numbers, IL-4 and IL-5 concentrations in the lung, total and allergen-specific 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-like receptor 4-deficient mice. Nicotine-free cigarette smoke also had significant anti-inflammatory effects on eosinophils, IL-4 and IL-5 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. CONCLUSION: Our experiments show that tCS exposure reduces allergen-induced 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-like receptor 4. The observed anti-Th2 effects of both nicotine and nicotine-free herbal cigarette smoke together suggests that tCS reduces the Th2 responses through nicotine and other products released by burning tobacco.
BACKGROUND:Patients with asthma who smoke have reduced lung function, increased exacerbation rates and increased steroid resistance compared to non-smoking asthmatics. In mice, cigarette smoke has been reported to have both pro- and anti-Th2 response effects. OBJECTIVE: We hypothesized that combining tobacco cigarette smoke (tCS) with allergen exposure increases inflammation, airway remodelling and lung function in mice. To test this hypothesis, we combined a severe triple allergen model with tCS exposure and investigated whether effects were due to Toll-like receptor 4 signalling and/or nicotine and also observed when nicotine-free cigarettes were used. METHODS: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 tCS during the allergen challenge period. Nicotine or nicotine-free herbal cigarette smoke was also applied to allergen challenged mice. RESULTS:tCS significantly reduced eosinophil numbers, IL-4 and IL-5 concentrations in the lung, total and allergen-specific 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-like receptor 4-deficient mice. Nicotine-free cigarette smoke also had significant anti-inflammatory effects on eosinophils, IL-4 and IL-5 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. CONCLUSION: Our experiments show that tCS exposure reduces allergen-induced 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-like receptor 4. The observed anti-Th2 effects of both nicotine and nicotine-free herbal cigarette smoke together suggests that tCS reduces the Th2 responses through nicotine and other products released by burning tobacco.
Authors: Arthur L Brody; Robert Hubert; Ryutaro Enoki; Lizette Y Garcia; Michael S Mamoun; Kyoji Okita; Edythe D London; Erika L Nurmi; Lauren C Seaman; Mark A Mandelkern Journal: Neuropsychopharmacology Date: 2017-03-06 Impact factor: 7.853
Authors: Tinne C J Mertens; Anne M van der Does; Loes E Kistemaker; Dennis K Ninaber; Christian Taube; Pieter S Hiemstra Journal: Physiol Rep Date: 2017-07-11
Authors: Carolin K Koss; Christian T Wohnhaas; Jonathan R Baker; Cornelia Tilp; Michèl Przibilla; Carmen Lerner; Silvia Frey; Martina Keck; Cara M M Williams; Daniel Peter; Meera Ramanujam; Jay Fine; Florian Gantner; Matthew Thomas; Peter J Barnes; Louise E Donnelly; Karim C El Kasmi Journal: Commun Biol Date: 2021-02-08
Authors: Martin Wepler; Jonathan M Preuss; Cornelia Tilp; Martina Keck; Jochen Blender; Ulrich Wachter; Tamara Merz; Josef Vogt; Sandra Kress; Michael Gröger; Andrea Hoffmann; Marina Fink; Enrico Calzia; Ute Burret; Peter Radermacher; Jan P Tuckermann; Sabine Vettorazzi Journal: Front Immunol Date: 2022-09-12 Impact factor: 8.786