Histopathologic features seen with different animal models following cutaneous sulfur mustard exposure

Abstract In an effort to understand the pathophysiology of sulfur mustard (2,2′ dichlorodiethyl sulfide, HD)-induced cutaneous lesions, a number of animal models have been used. Animal models have been and will continue to be used in the development of therapeutic strategies to protect against and/or moderate lesions, and to potentiate wound healing after HD exposure. Upon reviewing the histopathologic features seen after HD-exposure, we propose roles for different animal models in HD-research. Hematoxylin and eosin slides from protocols done originally as dose response studies for either liquid or vapor HD-exposures were examined. The animal models reported include the hairless guinea pig (HGP), weanling pig (WP), mouse ear (ME) and hairless mouse (HM). In all these animal models, HD induces subepidermal blister formation as well as epidermal cell death. The HGP appears to be the most sensitive model for epidermal necrosis. The HGP and, to a lesser degree, the HM react with a marked neutrophilic infiltrate. The ME provides a quantitative measure for HD effects and a mild inflammatory infiltrate similar to what is seen in human skin. Doses necessary to produce microblister formation in the WP are usually associated with more significant stromal and vascular changes than in other animal models. In addition to a quantitative measure of the HD effect and a mild inflammatory response, the cost, as well as the availability of specific antibodies, and DNA and RNA probes and primers gives the ME advantages for both drug screening and for the study of the pathophysiology of HD-induced cutaneous lesions. The sensitivity of the HGP and the abundant experience with vapor exposures establishes a place for this animal model in barrier cream and drug screening. The similarity of WP skin to human skin is important in the study of wound healing after HD exposure, as well as in the study of the pathophysiology of the cutaneous lesion and in more definitive therapeutic studies.