Effect of gamma-interferon on IL-1 alpha, beta and receptor antagonist production by normal human keratinocytes.

In inflammatory dermatoses, activated T cells produce interferon-gamma (IFN-gamma), which interacts with keratinocytes and contributes to the direct activation of these cells by inducing, among other factors, the expression of HLA-DR antigens and intercellular adhesion molecule-1. However, the action of IFN-gamma on epidermal cell cytokine production is not known. Our aim was to assess the effect of IFN-gamma on the production of IL-1 by normal human keratinocytes cultured in low calcium medium (MCDB153). In comparison with controls, the addition of non-toxic IFN-gamma concentrations (50-500 U/ml) to cell cultures induced a significant increase of IL-1 alpha and IL-1 beta production predominantly after 100 U/ml treatment in the cell extracts as well as in the supernatants at 24h and 48h. The production of the antagonist, IL-1RA, was also enhanced and the effect of the critical concentration (100 U/ml) was more evident. However, the absence of a characteristic dose response could not be explained by an antiproliferative effect of high IFN-gamma concentrations (250 and 500 U/ml) on cultured keratinocytes or by the induction of the nuclear stress protein, Hsp72, two phenomena known to down-regulate IL-1 biosynthesis. In conclusion, the modifications in keratinocyte IL-1 production under IFN-gamma stimulation can contribute to activate the epidermal cells and thus involve them in the local immune response.