Accession Number:

ADA443079

Title:

Sulfur Mustard- and Phosgene-Increased IL-8 in Human Small Airway Cell Cultures

Descriptive Note:

Technical rept.

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2004-04-01

Pagination or Media Count:

9.0

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 pgml and 965 - 181 pgml, 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 pgml to 628 - 105 593 - 69 pgml respectively. Chemical insult-induced increased IL-8 in SAC cultures provides an assay for screening countermeasures against the inhalation toxicity of chemical threat agents.

Subject Categories:

  • Toxicology
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE