Sulfur Mustard- and Phosgene- Increased IL-8 in Human Small Airway Cell Cultures: Implications for Medical Countermeasures Against Inhalation Toxicity
ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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Inflammation and edema are associated with respiratory and cutaneous exposure to sulfur mustard SM as well as with phosgene-induced lung injury. IL-8 is a key inflammatory cytokine that recruits neutrophils linked with the onset and progression of acute lung injury caused by inhalation of these chemical agents. In the present study, human lung small airway cell SAC cultures were exposed to either SM 25 to 400 micrometers or phosgene 0.1 to 6.4 ppm x min. IL-8 was increased after exposure to either SM or phosgene. At the optimum exposures for SM 100 micrometers and phosgene 1.6 ppm x min, IL-8 was increased by 1013 plus or minus 123 pgml and 965 plus or minus 181 pgml, respectively. Higher exposures to either agent increased cytotoxicity and decreased IL-8 levels. Ibuprofen has shown efficacy against phosgene pulmonary toxicity in mice. Ibuprofen 62, 125, 250, 500, 1000 micrometers significantly diminished phosgene-increased IL-8 in SAC cultures exposed to 2 ppm x min phosgene. Maximum inhibition of nearly 50 of phosgene-increased IL-8 was seen at 125 and 250 micrometers doses of ibuprofen from 1141 plus or minus 143 pgml to 628 plus or minus 105, 593 plus or minus 69 pgml respectively. Chemical insult-increased IL-8 in SAC cultures provides an assay for screening countermeasures against the inhalation toxicity of chemical threat agents. The increase in the inflammatory cytokine IL-8 by both SM and phosgene may further provide common pharmacological targets for drugs with Multi-Threat Medical Countermeasure MTMC action against distinct chemical threats.
- Chemical, Biological and Radiological Warfare