EFFECTS OF INTERFERONS ON TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION FROMHUMAN KERATINOCYTES

Interferons (IFNs) have been reported to have pleiotrophic effects inc luding the ability to induce the production of other cytokines in seve ral cell types, Tumour necrosis factor alpha (TNF-alpha) is pro-inflam matory cytokine a known to be produced by a variety of cells including human keratinocytes. In the present study, we sought to determine the effects of IFNs on TNF-alpha production from human keratinocytes. IFN -gamma (50-100 ng/ml) induced TNF-alpha production dose dependently, b ut no induction of TNF-alpha was observed with IFN-alpha or IFN-beta, Since in the epidermis cytokines often work with in a cascade fashion and keratinocytes are a source of primary cytokine, IL-1 alpha, whethe r combined treatment with TFN-gamma and IL-1 alpha had a synergistic e ffect on TNF-alpha. production was examined, Combined treatment with I FN-gamma (100 ng/ml) and IL-1 alpha (10 ng/ml) induced 2-3-fold higher level of TNF-alpha than IL-1 alpha alone, These results suggest that IFN-gamma is a positive regulator for the production of TNF-alpha from human keratinocytes and likely to increase skin inflammation. (C) 199 8 Academic Press.