Inflammatory cytokine response in sulfur mustard-exposed mouse skin.

Published on Jun 29, 2001in Journal of Applied Toxicology2.997
· DOI :10.1002/1099-1263(200012)20:1+<::AID-JAT685>3.0.CO;2-H
Karen M. Ricketts6
Estimated H-index: 6
(United States Army Medical Research Institute of Chemical Defense),
C. T. Santai1
Estimated H-index: 1
(United States Army Medical Research Institute of Chemical Defense)
+ 3 AuthorsRobert P. Casillas20
Estimated H-index: 20
(United States Army Medical Research Institute of Chemical Defense)
Assessment of anti-inflammatory therapies against sulfur-mustard (bis(2-chloroethyl)sulfide, HD)-induced skin injury has mainly relied on qualitative histopathological evaluation. Development of quantifiable inflammatory biomarkers using fast and reliable molecular methods is needed for screening anti-inflammatory drugs against HD injury. In this study, we used two different HD exposure models to determine the in vivo cutaneous response of the inflammatory cytokines interleukin-6 (IL-6), IL-lα, IL-1β and tumor necrosis factor alpha (TNF-α), in order to identify a suitable inflammatory biomarker common to both models. In the first model, the backs of hairless mice were exposed to HD vapor (1.4 g m -3 ) or sham controls for 6 min using an occluded vapor cup technique. In the second model, right ears of CD1 mice were exposed to a solution (5.0 μl of 195 mM) of HD (0.16 mg) in dichloromethane (CH 2 Cl 2 ) whereas left ears received only CH 2 Cl 2 (vehicle control). Sulfur-mustard-induced skin inflammation was assessed in skin punch specimens collected at time points up to 24 h post-exposure. Edema was determined by measuring tissue weight, and cytokine content was measured by enzyme immunosorbent assay. Characterized by an increase in edema and IL-6, HD provoked a cutaneous inflammatory response in both models beginning at 6 h post-exposure and continuing to 24 h. An increase in IL-lα was observed only in the hairless mouse model, also beginning at 6 h post-exposure and continuing to 24 h. No IL-1β or TNF-α response was observed at any time point in either exposure model. These data document the in vivo production of cutaneous IL-6, a distinct inflammatory biomarker, in two different HD exposure models. We conclude that IL-6 should be a useful in vivo biomarker for evaluating anti-inflammatory drugs against HD-induced skin injury.
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