PRODUCTION OF IL-10 BY MELANOMA-CELLS - EXAMINATION OF ITS ROLE IN IMMUNOSUPPRESSION MEDIATED BY MELANOMA

Previous studies have shown that IL-10 may modulate immune responses t owards the humoral arm by inhibiting production of cytokines involved in cell-mediated responses. In the present studies, we found that mRNA to IL-10 could be demonstrated in 66% of melanoma cell lines by PCR a mplification of reverse-transcribed mRNA and in supernatants of the ce ll lines by ELISA. Release into the supernatants increased approximate ly 2-fold each day up to 3 days. The MW of S-35-labelled IL-10 secrete d by melanoma cells was similar to that reported in previous studies. In the present studies we also examined whether IL-10 may be responsib le for some of the immunosuppressive effects of the melanoma cell supe rnatants observed in previous studies, by testing whether MAbs against IL-10 could reverse the inhibitory effects of these supernatants. Rec ombinant IL-10 and melanoma supernatants were found to inhibit product ion of TNF-alpha, IFN-gamma, IL-2 and mixed lymphocyte reactions but r eversal of these effects of melanoma supernatants by MAbs against IL-1 0 was only seen in the case of TNF-alpha production. These results ext end the range of cell types known to produce IL-10 and indicate that m alignancy of certain cell types may lead to unregulated production of IL-10 that could have the potential to modulate immune responses again st the tumor. (C) 1994 Wiley-Liss, Inc.