Barrier function coordinately regulates epidermal IL-1 and IL-1 receptor antagonist mRNA levels

Disruption of the cutaneous permeability barrier increases mRNA levels for TNF, GM-CSF, IL-1 alpha, and IL-1 beta in the epidermis. We have hypothesized that the cytokines mediate the changes in lipid and DNA synthesis which occur following barrier disruption. To further characterize the cytokine response to barrier abrogation, we examined the levels of epidermal IL-1ra mRNA in two acute models and one chronic model in the hairless mouse. IL-1ra mRNA levels increased shortly after acute disruption of the barrier with acetone, reached a peak at 3-4 h after treatment, and returned to control levels by 8h. These changes in mRNA levels parallel those which occur for IL-1 alpha and beta. Furthermore, IL-1ra mRNA levels were elevated 5-fold and 4-fold, at 2.5 h and 4 h, respectively, following tape-stripping, a second acute model of barrier disruption. Finally, IL-1ra mRNA levels were elevated 2.5-fold in the epidermis of EFAD mice, which have a chronic barrier defect. Thus, the cutaneous response to barrier disruption includes mechanisms which increase IL-1 and IL-1ra mRNA levels in a coordinate manner. The net result provides a regulatory mechanism for controlling the biological effects of increased IL-1 production.