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Modulation of cytokine gene expression by anti-inflammatory agents following <i>in vivo</i> sulfur mustard injury

TitleModulation of cytokine gene expression by anti-inflammatory agents following in vivo sulfur mustard injury
Publication TypeConference Proceedings
Year of Conference2003
AuthorsSabourin C.L., Stonerock M.L., Niemuth N.A., Kiser R.C., Casbohm S.L., Casillas R.P., Babin M.C., Schlager J.J.
Conference NameProceedings of the 42nd Annual Meeting of the Society of Toxicology
Volume72 (S-1)
PublisherOxford University Press
Conference LocationSalt Lake City, UT
KeywordsSulfur Mustard

Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a chemical warfare agent that penetrates the skin rapidly and causes extensive blistering after a latent period. We have used the mouse ear vesicant model for cutaneous SM injury quantitation to evaluate pharmacological agents in a number of drug classes, including anti-inflammatory drugs. Topically applied anti-inflammatory agents, including indomethacin and vanilloids, have been shown to reduce SM-induced skin inflammation and tissue damage. We previously identified an early increase in the in vivo expression of the inflammatory cytokines GM-CSF, IL-1b, and IL-6 following murine cutaneous exposure to SM. The goal of this study was to determine the effect of topically administered anti-inflammatory agents in reversing inflammatory mediator gene expression following SM-induced injury. Alterations in mouse (n=6) cutaneous GMCSF, IL-1b, and IL-6 gene expression from ears with and without pre-treatment with indomethacin, heptylisovanillamide, and octyl homovanillamide were examined using real time quantitative RT-PCR. Indomethacin pretreatment produced a significant reduction in the SM-mediated increase of IL-1band IL-6 mRNA levels. Heptylisovanillamide pretreatment produced significant reductions of GM-CSF, IL-1b, and IL-6 mRNA levels. Octyl homovanillamide produced an apparent reduction of cytokine mRNA levels; however, the reduction did not reach statistical significance at the present animals numbers. SM-induced inflammation was significantly modulated by all three anti-inflammatory agents as determined by reduction in tissue edema (n=10). The alteration in cytokine gene expression suggests that these drugs play a role in modulating SM-induced injury by reducing inflammatory pathways. Supported by the US Army Medical Research and Materiel Command under Contract No. DAMD17-99-D-0010, Task Order 0002.

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