Time course of lewisite-induced skin lesions and inflammatory response in the SKH-1 hairless mouse model.

ABSTRACT

Data on the toxicity of lewisite (L), a vesicant chemical warfare agent, are scarce and conflicting, and the use of the specific antidote is not without drawbacks. This study was designed to evaluate if the SKH-1 hairless mouse model was suitable to study the L-induced skin injuries. We studied the progression of lesions following exposure to L vapors for 21 days using paraclinical parameters (color, transepidermal water loss (TEWL), and biomechanical measurements), histological assessments, and biochemical indexes of inflammation. Some data were also obtained over 27 weeks. The development of lesions was similar to that reported in other models. The TEWL parameter appeared to be the most appropriate index to follow their progression. Histological analysis showed inflammatory cell infiltration and microvesications at day 1 and a complete wound closure by day 21. Biochemical studies indicated a deregulation of the levels of several cytokines and receptors involved in inflammation. An increase in the quantity of pro-matrix metalloproteinases 2 and 9 was shown as observed in other models. This suggests that the SKH-1 mouse model is relevant for the investigation of the physiopathological process of skin lesions induced by L and to screen new treatment candidates.