BIOLOGICAL-ACTIVITY OF HUMAN EPIDERMAL INTERLEUKIN-1BETA - COMPARISONWITH RECOMBINANT HUMAN INTERLEUKIN-1BETA

We have recently presented evidence that human plantar stratum corneum and psoriatic scales contain biologically active interleukin-1beta (I L-1 beta) which has been activated in a process not involving interleu kin-1 beta-converting-enzyme. The aim of the present study was to comp are this form of native IL-1 beta with recombinant mature human IL-1 b eta as regards activity and the effects of inhibitors. In an assay bas ed on the ability of IL-1 to induce the expression of E-selectin in cu ltured endothelial cells, the maximal activity of IL-1 beta partially purified from plantar stratum corneum and recombinant IL-1 beta was ap proximately the same. The specific activity was slightly higher for re combinant IL-1 beta, although this difference was within one order of magnitude. An antibody to IL-1 beta caused total inhibition of both fo rms of IL-1 beta with no significant differences in the dose-response curves for the antibody. Immunochemical analyses and experiments with neutralising antibodies specific for IL-1 alpha and tumor necrosis fac tor-alpha (TNF-alpha) verified that the observed activity in the parti ally purified preparation was due to IL-1 beta, and not to IL-1 alpha or TNF-alpha. There were no significant differences between the two fo rms of IL-1 beta as regards the inhibitory effects of recombinant IL-1 receptor antagonist. Partially purified IL-1 beta from plantar stratu m corneum and from psoriatic scales were both highly active in the D10 proliferation assay. This activity could be totally inhibited with an IL-1 beta specific antibody. This work thus confirms the presence of biologically active IL-1 beta in plantar stratum corneum and psoriatic scales. Alternatively activated IL-1 beta in the epidermis should be considered in future studies on skin biology and pathophysiology.