Tiotropium Attenuates Virus-Induced Pulmonary Inflammation in Cigarette Smoke–Exposed Mice
| Autor: | Cornelia Tilp, Birgit Jung, Klaus J. Erb, Matthias J. Duechs, Hannes Bucher |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
medicine.medical_treatment
viruses Anti-Inflammatory Agents Down-Regulation Cell Count Choline O-Acetyltransferase 03 medical and health sciences Mice 0302 clinical medicine Influenza A Virus H1N1 Subtype Smoke Tobacco medicine Animals 030212 general & internal medicine Respiratory system Tiotropium Bromide Lung Roflumilast Fluticasone Pharmacology COPD business.industry Body Weight Oxo-Acid-Lyases Tiotropium bromide Pneumonia respiratory system Inflammation Immunopharmacology and Asthma medicine.disease respiratory tract diseases Respiratory Syncytial Viruses Mice Inbred C57BL Cytokine medicine.anatomical_structure 030228 respiratory system Immunology Molecular Medicine Cytokines Female business Viral load medicine.drug |
| Zdroj: | The Journal of Pharmacology and Experimental Therapeutics |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Viral infections trigger exacerbations in chronic obstructive pulmonary disease (COPD), and tiotropium, a M3 receptor antagonist, reduces exacerbations in patients by unknown mechanisms. In this report, we investigated whether tiotropium has anti-inflammatory effects in mice exposed to cigarette smoke (CS) and infected with influenza virus A/PR/8/34 (H1N1) or respiratory syncytial virus (RSV) and compared these effects with those of steroid fluticasone and PDE4-inhibitor roflumilast. Mice were exposed to CS; infected with H1N1 or RSV; and treated with tiotropium, fluticasone, or roflumilast. The amount of cells and cytokine levels in the airways, lung function, and viral load was determined. NCI-H292 cells were infected with H1N1 or RSV and treated with the drugs. In CS/H1N1-exposed mice, tiotropium reduced neutrophil and macrophage numbers and levels of interleukin-6 (IL-6) and interferon-γ (IFN-γ) in the airways and improved lung function. In contrast, fluticasone increased the loss of body weight; failed to reduce neutrophil or macrophage numbers; increased IL-6, KC, and tumor necrosis factor-α (TNF-α) in the lungs; and worsened lung function. Treatment with roflumilast reduced macrophage numbers, IL-6, and KC in the lungs but had no effect on neutrophil numbers or lung function. In CS/RSV-exposed mice, treatment with tiotropium, but not fluticasone or roflumilast, reduced neutrophil numbers and IL-6 and TNF-α levels in the lungs. Viral load of H1N1 and RSV was significantly elevated in CS/virus-exposed mice and NCI-H292 cells after fluticasone treatment, whereas tiotropium and roflumilast had no effect. In conclusion, tiotropium has anti-inflammatory effects on CS/virus-induced inflammation in mice that are superior to the effects of roflumilast and fluticasone. This finding might help to explain the observed reduction of exacerbation rates in COPD patients. |
| Databáze: | OpenAIRE |
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