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Estimation of neutrophil infiltration into hairless guinea pig skin treated with 2,2' -dichlorodiethyl sulfide

Abstract : Despite growing acceptance of the hairless guinea pig (HPG) for evaluating sulfur mustard (2,2'dichlorodiethylsulfide, HD) skin injury, there are presently few antivesicant drug assessment endpoints validated in vivo for this model. We measured the activity of myeloperoxidase (MPO) to characterize the dose- and time-dependence of polymorphonuclear leukocyte (PMN) infiltration during development of the HD lesion. Biopsies were obtained from the dorsal thoracic-lumbar area of HGPs at successive 3 hr time intervals for up to 24 hrs following controlled exposure to either 5, 7, 8 or 10 min HD vapor. The presence of PMNs, as judged by MPO levels, peaked at 9 hrs irrespective of total HD vapor dose. The maximum response was a 20-fold increase compared to unexposed control sites at 9 hrs following 10 min HD vapor. This time period coincides with epidermal detachment characterized previously by electron microscopy in the HGP. By 24 hrs post-exposure, the MPO levels subsided markedly (2-fold compared to controls). These results suggest that PMNs participate in the HGP cutaneous inflammatory response following exposure to HD and that MPO may be a useful biological marker for evaluating putative antivesicants.