Zhang, Z., J. E. Riviere, and N.A. Monteiro-Riviere. Topical Sulfur Mustard Induces Changes in Prostaglandins and Interleukin-1a in Isolated Perfused Porcine Skin. In Vitro Toxicol. 1995. 8(2): 149-158.

sulfur mustard - 00505-60-2

Sulfur mustard [bis(2-chloroethyl) sulfide, HD] is an alkylating agent that causes severe cutaneous injury. The isolated perfused porcine skin flap (IPPSF) is an in vitro model that has been utilized in cutaneous toxicity research. The objective of this study was to characterize the local IPPSF inflammatory response after topical exposure to 5.0 and 10.0 mg/ml of HD (n=5/treatment, n=5/control). Biochemical markers of viability [cumulative glucose utilization (CGU)], vascular resistance (VR), morphological parameters, and venous flux of prostaglandin E₂, prostaglandin F_2a (PGF_2a ), and interleukin 1a (IL-1a ) were determined. HD caused a dose-related response in the formation of gross blisters, and epidermal-dermal separation. Decreases in CGU and an increase in VR were seen in all HD-treated IPPSFs. Increase of both PGE₂ and PGF_2a was observed only in 5.0 mg/ml HD treatment, which showed the greatest increase in VR, while the 10.0 mg/ml concentration of HD enhanced the release of IL-1a . These results suggest that HD is a potent dermal toxic agent that induces alterations in glucose metabolism and vascular resistance, which resulted in dose-specific patterns of PGE₂, PGF_2a and IL-1a release.