The effect of smoking cessation and steroid treatment on emphysema in guinea pigs

• Published in: Respiratory medicine Vol. 101; no. 11; pp. 2327 - 2335
• Main Authors: Milot, Julie, Meshi, Bernard, Taher Shabani Rad, Meer, Holding, Gemma, Mortazavi, Niloufar, Hayashi, Shizu, Hogg, James C
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.2007; Elsevier; Elsevier Limited
• Subjects: Adenoviridae Infections - complications; Adenovirus; Adenoviruses; Animals; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chronic obstructive pulmonary disease, asthma; Cigarette; Cytokine; Dexamethasone - therapeutic use; Drug Resistance; Emphysema; Female; Guinea pig; Guinea Pigs; Hogs; Immunologic Techniques; Inflammation Mediators - metabolism; Leukocyte Count; Lung - pathology; Lungs; Lymphocytes; Medical research; Medical sciences; Neutrophils; Pharmacology. Drug treatments; Pneumology; Pneumonia - drug therapy; Pneumonia - etiology; Pneumonia - pathology; Proteins; Pulmonary Emphysema - drug therapy; Pulmonary Emphysema - etiology; Pulmonary Emphysema - pathology; Pulmonary/Respiratory; Random Allocation; Rodents; Smoking - adverse effects; Smoking Cessation; Tobacco, tobacco smoking; Toxicology; Virus Latency; Cigarette; Guinea pig; Adenovirus; Emphysema; Cytokine; Steroid; Lung disease; Corticosteroid; Adenoviridae; Poison withdrawal; Respiratory disease; Rodentia; Tobacco smoking; Virus; Vertebrata; Tobacco; Mammalia; Treatment; Shutdown; Animal; Bronchus disease; Obstructive pulmonary disease; Immunosuppressive agent; Pneumology
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2007.06.022

Summary Background Emphysema induced by cigarette smoking is characterized by an inflammatory process, which is resistant to steroid and remains active in lung tissue long after smoking has stopped. Latent adenoviral infection (Ad5) increases emphysema development and the inflammatory response to cigarette smoke and, in allergic lung inflammation, suppresses anti-inflammatory effects of steroids. Objectives The present study was designed to examine the effect of smoking cessation and steroid treatment on lung emphysema and inflammation in a guinea pig model of emphysema and to determine if latent adenoviral infection induces resistance to the inflammatory effects of steroid. Methods Latent adenovirus or sham infected animals exposed to room air or cigarette smoke for 16 weeks were either sacrificed immediately or treated with dexamethasone or diluent for an additional 5 weeks without smoke exposure. Lung morphometry, inflammatory cells and mediators were studied. Results Smoking cessation was associated with an increase in lung surface area and surface area to volume ratio. Smoking cessation was also associated with decreases in lung neutrophils, CD4 cells, and IL-8, RANTES and IFN- γ mRNAs to control levels. Steroid treatment significantly lowered neutrophils, eosinophils and IFN- γ mRNA and, while adenoviral infection did not alter these steroid-induced changes, it independently increased airway wall neutrophils and CD8 cells. Conclusion smoking cessation decreases lung inflammation and latent adenoviral infection does not induce steroid resistance in this animal model.