Colchicine decreases airway hyperreactivity after phosgene exposure.
Phosgene (COCl(2)) exposure affects an influx of inflammatory cells into the lung, which can be reduced in an animal model by pretreatment with colchicine. Inflammation in the respiratory tract can be associated with an increase in airway hyperreactivity. We tested the hypotheses that (1) phosgene exposure increases airway reactivity and (2) colchicine can decrease this elevation. Sprague Dawley rats (70 d old; male) were exposed to 1 ppm COCl(2) for 1 h. Airway reactivity was tested at 0, 4, and 24 h postexposure by infusing anesthetized animals intravenously with acetylcholine and assessing expiratory resistance and dynamic compliance. Immediately and 4 h postexposure, a significant change in expiratory resistance and dynamic compliance was observed in those animals exposed to COCl(2), while at 24 h this response was greater. A second experiment was performed in rats pretreated with colchicine (1 mg/kg) or saline given intraperitoneally, exposed to 1 ppm COCl(2) for 1 h, with both expiratory resistance and dynamic compliance assessed at 24 h. After exposure, cell differentials and protein in lavage were also quantitated. The results indicate that colchicine decreased neutrophil influx, protein accumulation, and changes in both expiratory resistance and dynamic compliance after COCl(2) exposure. Colchicine may affect injury and changes in expiratory resistance and dynamic compliance by diminishing the incursion of inflammatory cells, but other properties of this medication may also be responsible for the observed results.
Ghio
Andrew
A
National Health Effects and Environmental Research Laboratory U.S. Environmental Protection Agency, Office of Research and Development, Research Triangle Park, NC 27599, USA. ghio.andy@epa.gov
Lehmann
James
J
Winsett
Darrell
D
Richards
Judy
J
Costa
Daniel
D
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D018893:Bronchoalveolar Lavage / Q000379:methods; D003078:Colchicine / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005540:Forced Expiratory Flow Rates / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D019570:Inhalation Exposure; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000648:ultrastructure; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010705:Phosgene / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010705:Phosgene; D000109:Acetylcholine; D003078:Colchicine