Acute disruption of the permeability barrier produces marked changes in epidermal metabolism, including increased lipid synthesis, increased DNA synthesis, and the enhanced production of cytokines. Because abnormalities in the barrier are present in a wide variety of skin disorders, 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 treatment 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 and duration of barrier disruption. Likewise, the epidermal mitotic index, which was localized to the basal layer, increased with repeated disruption, indicating that the hyperplasia could be ascribed to increased cell proliferation. However, occlusion with a water-impermeable membrane, which prevents water loss, did not prevent the epidermal hyperplasia. Moreover, immunohistochemical staining for TNF alpha and IL 1 alpha increased following repeated acetone treatment or tape stripping, and this increase also was not blocked by occlusion. These studies indicate that manipulations of the stratum corneum which disrupt the permeability barrier, such as repeated acetone treatment or tape stripping, induce a variety of biologic responses in the underlying epidermis. Since neither the increase in epidermal cytokine production nor the described changes in cutaneous pathology were prevented by occlusion, in these two models the changes should not be attributed to increased water loss, but rather to epidermal injury resulting in the production and release of epidermal cytokines.
