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

Abstract

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. 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. 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. 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-gamma mRNAs to control levels. Steroid treatment significantly lowered neutrophils, eosinophils and IFN-gamma mRNA and, while adenoviral infection did not alter these steroid-induced changes, it independently increased airway wall neutrophils and CD8 cells. Smoking cessation decreases lung inflammation and latent adenoviral infection does not induce steroid resistance in this animal model.