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


OBJECTIVE
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-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.


CONCLUSIONS
Smoking cessation decreases lung inflammation and latent adenoviral infection does not induce steroid resistance in this animal model.
Milot
Julie
J
Hôpital Laval, Institut universitaire de cardiologie et de pneumologie, 2725 chemin Ste-Foy, Québec, Canada G1V 4G5. julie.milot@crhl.ulaval.ca
Meshi
Bernard
B
Taher Shabani Rad
Meer
M
Holding
Gemma
G
Mortazavi
Niloufar
N
Hayashi
Shizu
S
Hogg
James C
JC
D000257:Adenoviridae Infections / Q000150:complications; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006168:Guinea Pigs; D007158:Immunologic Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D009504:Neutrophils; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011897:Random Allocation; D012907:Smoking / Q000009:adverse effects; D016540:Smoking Cessation; D017735:Virus Latency
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D003907:Dexamethasone