Reduction of neutrophil influx diminishes lung injury and mortality following phosgene inhalation.
Ghio-AJ; Kennedy-TP; Hatch-GE; Tepper-JS
J Appl Physiol 1991 Aug; 71(2):657-665
The role of neutrophils in lung injury resulting from phosgene (75445) exposure was studied by inhibiting neutrophil function with cyclophosphamide, the lipoxygenase inhibitor AA861, and colchicine. Male Sprague-Dawley-rats were treated with cyclophosphamide 4 days and 1 day prior to exposure phosgene; AA861 24 hours, 12 hours, or immediately before phosgene; colchicine 1 hour before phosgene; cyclophosphamide and colchicine in combination prior to phosgene; or colchicine 30 minutes after phosgene. Rats were exposed to 0.5 parts per million (ppm) phosgene for 60 minutes. Phosgene exposure caused increases in lavage fluid protein, leukotriene-B4 (LTB4), and thiobarbituric-acid reactive products (TBA), as well as a decrease in lung volume. Cyclophosphamide, AA861 and colchicine decreased leukocyte and neutrophil counts in the blood and influx into the lung after phosgene, along with protein and TBA reactive products in the lavage fluid. Cyclophosphamide and colchicine administered together did not show an advantage over either used alone. When given after phosgene exposure, colchicine reduced neutrophil influx and TBA reactive products in the lavage fluid. The effects of the three treatments on mortality was examined using female CD-1-mice exposed to 2.0ppm phosgene for 90 minutes and treated with cyclophosphamide, AA861, and colchicine according to protocols similar to those used for rats. All of the treatments significantly decreased mortality after phosgene exposure. The authors conclude that the influx of neutrophils into the lungs that occurs after phosgene exposure may be prevented with colchicine, and this compound may be useful as a therapeutic agent in phosgene poisoning.
NIOSH-Publication; NIOSH-Grant; Pulmonary-system-disorders; Toxic-gases; Toxic-effects; Lung-disorders; Laboratory-animals; Respiratory-system-disorders; Chlorine-compounds
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Journal of Applied Physiology
University of Tenn Center Health Scien, Memphis, Tennessee