THE EPIDERMAL HYPERPLASIA ASSOCIATED WITH REPEATED BARRIER DISRUPTIONBY ACETONE TREATMENT OR TAPE STRIPPING CANNOT BE ATTRIBUTED TO INCREASED WATER-LOSS

Acute disruption of the permeability barrier produces marked changes i n epidermal metabolism, including increased lipid synthesis, increased DNA synthesis, and the enhanced production of cytokines. Because abno rmalities in the barrier are present in a wide variety of skin disorde rs, we hypothesized that barrier disruption may be an important event that initiates pathological changes in the skin. In the present study, we found that repeated barrier disruption by topical acetone treatmen t or tape stripping induced epidermal hyperplasia in the flank skin of hairless mice and the ear of ICR mice, as well as inflammation in ear skin. The degree of epidermal hyperplasia correlated with the level a nd duration of barrier disruption. Likewise, the epidermal mitotic ind ex, which was localized to the basal layer, increased with repeated di sruption, indicating that the hyperplasia could be ascribed to increas ed cell proliferation. However, occlusion with a water-impermeable mem brane, which prevents water loss, did not prevent the epidermal hyperp lasia. Moreover, immunohistochemical staining for TNF alpha and IL 1 a lpha increased following repeated acetone treatment or tape stripping, and this increase also was not blocked by occlusion. These studies in dicate that manipulations of the stratum corneum which disrupt the per meability barrier, such as repeated acetone treatment or tape strippin g, induce a variety of biologic responses in the underlying epidermis. Since neither the increase in epidermal cytokine production nor the d escribed changes in cutaneous pathology were prevented by occlusion, i n these two models the changes should not be attributed to increased w ater loss, but rather to epidermal injury resulting in the production and release of epidermal cytokines.