Skin Models Used to Define Mechanisms of Action of Sulfur Mustard

Abstract

Sulfur mustard (SM) is a threat to both civilian and military populations. Human skin is highly sensitive to SM causing delayed erythema, edema and inflammatory cell infiltration, followed by the appearance of large fluid filled blisters. Skin wound repair is prolonged following blistering which can result in impaired barrier function. Key to understanding the action of SM in the skin is the development of animal models that have a pathophysiology comparable to humans such that quantitative assessments of therapeutic drugs efficacy can be assessed. Two animal models, hairless guinea pigs and swine, are preferred to evaluate dermal products because their skin is morphologically similar to human skin. In these animal models, SM induces degradation of epidermal and dermal tissues, but does not induce overt blistering, only microblistering. Mechanisms of wound healing are distinct in these animal models. Whereas guinea pig heals by contraction, in swine, like humans, skin heals by re-epithelialization. Mice, rats and rabbits are also used for SM mechanistic studies. However, healing is also mediated by contraction, moreover, only microblistering is observed. Improvements in animal models are essential for the development of therapeutics to mitigate toxicity resulting from dermal exposure to SM.