Interleukin‐10 production by human carcinoma cell lines and its relationship to interleukin‐6 expression

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Abstract
Recent data indicate a major role for IL‐10 in suppressing immune and inflammatory reactions. To date, expression of human IL‐10 has been attributed primarily to helper T lymphocytes, activated monocytes, and neoplastic B cells, and was often found to be associated with IL‐6 expression. In this study we sought to determine whether non‐hematopoietic human tumor cell lines produce IL‐10 and, if so, what is the relationship 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 carcinomas of the kidney, colon, breast and pancreas, malignant melanomas and neuroblastomas. IL‐6 protein was secreted by 28 of the tumor ceil lines; IL‐10 was measurable in 15 cell lines. IL‐6 secretion was maximal and most frequent in renal‐cancer cell lines, while IL‐10 production was found to be highest and most common among cell lines derived from colon carcinomas. IL‐10 in conditioned medium of one of the colon carcinoma cell lines (CCL222) was bio‐active, as demonstrated in the mouse 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 monoclonal antibody. Expression of IL‐6 and IL‐10 was confirmed by RNA analysis 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 colon‐carcinoma cells. IL‐10 secretion by colon‐carcinoma cells was moderately 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 types of human carcinomas are capable of expressing and releasing IL‐6 and/or IL‐10, suggesting a role of these cytokines in solid‐tumor development and anti‐tumor immunity.

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