Sulfur Mustard- and Phosgene- Increased Il-8 in Human Small Airway Cell Cultures: Implications for Medical Countermeasures against Inhalation Toxicity

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 μM] or phosgene [0.1 to 6.4 ppm • min]. IL-8 was increased after exposure to either SM or phosgene. At the optimum exposures for SM (100 μM) and phosgene (1.6 ppm • min), IL-8 was increased by 1013 +123 pg/ml and 965 +181 pg/ml, 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 μM) significantly diminished phosgene-increased IL-8 in SAC cultures exposed to 2 ppm • min phosgene. Maximum inhibition of nearly 50% of phosgene-increased IL-8 was seen at 125 and 250 μM doses of ibuprofen (from 1141 +143 pg/ml to 628 +105, 593 +69 pg/ml 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.