Sulfur Mustard- and Phosgene-Increased IL-8 in Human Small Airway Cell Cultures
Abstract
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 chemotactic inflammatory cytokine that recruits neutrophils and contributes to 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 * min. IL-8 was increased after exposure to either SM or phosgene. In SAC cultures exposed to SM (100 micrometers) and phosgene (1.6 ppm * min), IL-8 was increased above controls by 1013 +/- 123 pg/ml and 965 +/- 181 pg/ml, respectively. Exposure to higher concentrations of either agent increased cytotoxicity and reduced IL-8 towards levels observed in unexposed control SAC. 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 * min phosgene. Maximum inhibition of nearly 50% of phosgene increased IL-8 was seen at 125 and 250 micrometer doses of ibuprofen (from 1141 +/- 143 pg/ml to 628 +/- 105 593 +/- 69 pg/ml respectively). Chemical insult-induced increased IL-8 in SAC cultures provides an assay for screening countermeasures against the inhalation toxicity of chemical threat agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA443079
Entities
People
- A. D. Williams
- A. M. Sciuto
- F. M. Cowan
- M. M. Paris
- T. S. Moran
- W. J. Smith
Organizations
- United States Army Medical Research Institute of Chemical Defense