INTERLEUKIN-10 PRODUCTION BY HUMAN CARCINOMA CELL-LINES AND ITS RELATIONSHIP TO INTERLEUKIN-6 EXPRESSION

Recent data indicate a major role for IL-10 in suppressing immune and inflammatory reactions. To date, expression of human IL-10 has been at tributed primarily to helper T lymphocytes, activated monocytes, and n eoplastic B cells, and was often found to be associated with IL-6 expr ession. In this study we sought to determine whether non-hematopoietic human tumor cell lines produce IL-10 and, if so, what is the relation ship between IL-10 and IL-6. Using ELISA, we determined IL-10 and IL-6 levels in culture supernatants of 48 cell lines established from carc inomas of the kidney, colon, breast and pancreas, malignant melanomas and neuroblastomas. IL-6 protein was secreted by 28 of the tumor cell lines; IL-10 was measurable in 15 cell lines. IL-6 secretion was maxim al and most frequent in renal-cancer cell lines, while IL-10 productio n was found to be highest and most common among cell lines derived fro m colon carcinomas. IL-10 in conditioned medium of one of the colon ca rcinoma cell lines (CCL222) was bio-active, as demonstrated in the mou se MC/9 mast-cell-line assay and in human mixed-lymphocyte reactions. In both assays, IL-10 bio-activity was neutralized by an anti-IL-10 mo noclonal antibody. Expression of IL-6 and IL-10 was confirmed by RNA a nalysis using message amplification by PCR and sequencing of amplified cDNA. LPS, IL-1 alpha, and TNF-alpha strongly enhanced the release of IL-6 by RCC cells, but only marginally affected IL-10 production in c olon-carcinoma cells. IL-10 secretion by colon-carcinoma cells was mod erately stimulated by IFN-gamma and IL-4. Dexamethasone suppressed the release of IL-6, but had no inhibitory effect on IL-10 secretion. Our results demonstrate that tumor cell lines established from certain ty pes of human carcinomas are capable of expressing and releasing IL-6 a nd/or IL-10, suggesting a role of these cytokines in solid-tumor devel opment and anti-tumor immunity. (C) 1993 Wiley-Liss, Inc.