Inflammatory cytokine response in sulfur mustard‐exposed mouse skin † ‡

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‐1α,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‐1α 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. Published in 2000 by John Wiley & Sons, Ltd.