Tiotropium effects on airway inflammatory events in the cat as an animal model for acute cigarette smoke-induced lung inflammation

Exp Lung Res. 2014 Aug;40(6):272-87. doi: 10.3109/01902148.2014.905657. Epub 2014 May 2.

Abstract

Background: Chronic obstructive pulmonary disease is an inflammatory lung disease mainly caused by tobacco smoke inhalation.

Methods: Fifteen healthy adult male cats were categorized into 3 groups: (1) control group, (2) exposed to cigarette smoke (CS), and (3) exposed to CS treated with tiotropium.

Results: Increases in clinical signs and airway responsiveness in CS cats were found compared to control animals. The airway hyperresponsiveness and clinical signs were significantly attenuated by treatment with tiotropium. The CS-induced pulmonary release of interleukin-6, interleukin-8, monocyte chemotactic protein-1, and tumor necrosis factor alpha was reduced in the tiotropium group. Exposure to CS significantly increased total inflammatory cells number in bronchoalveolar lavage fluid, which was significantly attenuated by treatment with tiotropium. The number of macrophages, eosinophils and neutrophils and lymphocytes was increased after exposure to CS. Tiotropium significantly reduced the number of all these cells. Perivascular, peribronchiolar infiltration of inflammatory cells and Reid index increased in the CS group. Treatment with tiotropium significantly reduced these parameters to control level. Enhanced lipid peroxidation with concomitant reduction of antioxidants status was observed in the CS group. Tiotropium significantly reduced the serum, lung lavage, lung, and tracheal tissue lipid peroxides to near control levels. Tiotropium also decreased lung and tracheal protein leakage, and prevented the reduction of total antioxidant status in serum, lung lavage, lung and tracheal tissue of the CS group.

Conclusion: Cigarette smoke increases airway responsiveness and inflammation in a cat model of CS induced lung inflammation. It can effectively be reduced by treatment with tiotropium.

Keywords: animal model; cat; cigarette smoke; lung inflammation; tiotropium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Bronchoalveolar Lavage Fluid
  • Cats
  • Chemokine CCL2 / metabolism
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Eosinophils / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Lipid Peroxidation / drug effects
  • Lipid Peroxides / metabolism
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Pneumonia / drug therapy*
  • Pneumonia / etiology*
  • Pneumonia / metabolism
  • Scopolamine Derivatives / pharmacology*
  • Smoke / adverse effects*
  • Smoking / adverse effects*
  • Tiotropium Bromide
  • Tobacco Products / adverse effects*
  • Trachea / drug effects
  • Trachea / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antioxidants
  • Chemokine CCL2
  • Interleukin-6
  • Interleukin-8
  • Lipid Peroxides
  • Scopolamine Derivatives
  • Smoke
  • Tumor Necrosis Factor-alpha
  • Tiotropium Bromide