The anti-inflammatory and anti-remodeling effect of tiotropium bromide in the subacute cigarette exposure mouse model

ERALDEMİR F. C. , Sengul A., Ozkan M., Kokturk S., Ozsoy D. , Yildiz F. A.

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, vol.9, no.11, pp.22824-22834, 2016 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 9 Issue: 11
  • Publication Date: 2016
  • Page Numbers: pp.22824-22834


Chronic obstructive pulmonary disease is an inflammatory lung disease mainly caused by cigarette smoke inhalation. We aimed to evaluate the effect of tiotropium bromide, which is an anticholinergic bronchodilator, on inflammation and remodeling in the subacute cigarette exposure mice model. Thirty-five healthy 25-40 g male balbc mice were categorized into 3 groups: control group (n=7), those exposed to cigarette smoke (n=18), and those exposed to cigarette smoke and treated with tiotropium bromide (n=10). After 5 weeks, tiotropium or saline was administered to mice for a period of two weeks by inhalation. The mice were anesthetized, bronchoalveolar lavage was performed and lung tissues removed. Interleukin-1 beta (IL-1 beta), macrophage inflammatory protein-1 alpha (MIP-1 alpha), tumor necrosis factor a (TNF-alpha) measurements were made in BAL fluid. The lung tissues were fixated and sections were stained for morphological evaluation of the lung tissues. The presence of cells undergoing apoptosis and the macrophages were determined by immunohistochemical detection of caspase-3 and MAC387. We found that cigarette exposure significantly increased the IL-1 beta, TNF-alpha and MIP-1 alpha levels. Furthermore, tiotropium significantly improved the IL-1 beta, TNF-alpha and MIP-1 alpha levels (P<0.05). The smoke exposure group exhibited an increased thickness of the alveolar wall, pulmonary edema and hemorrhage, as well as infiltration of the inflammatory cells into the alveolar spaces. In the Thio group the interstitial fibrosis and inflammation were decreased compared to the smoke group. The numbers of MAC387-labeled cells and the caspase-3-labeled cells were higher in the smoke group than in the other groups (P<0.0001). Besides its bronchodilator effect, tiotropium may be a promising therapeutic choice to control inflammation and remodeling due to cigarette exposure.