IL-6 and IFN-gamma regulation of IL-10 production by human colon carcinomacells

IL-10 has been shown to play a crucial role inl immunosuppression in cancer patients. We explored the regulation of IL-10 production by TNF-alpha, IL- 1 beta, IL-6, IL-8, and IFN-gamma in human colon carcinoma COLO205 cells. N orthern analysis revealed a marked expression of IL-10 mRNA after stimulati on by IL-6, and a marginal but significant expression by TNF-alpha, IL-1 be ta or IFN-gamma. No IL-10 mRNA expiession was observed when cells were untr eated or incubated with IL-8. IL-10 in the culture supernatants showed good agreement with mRNA expression. In addition, IFN-gamma dose-dependently in hibited this IL-6-induced production of IL-10. MTT assay revealed that low dose IFN-gamma (1-10 ng/ml) had no effect on growth of COLO205 cells, but t hat high dose IFN-gamma (>100 ng/ml) significantly inhibited their prolifer ation. Northern analysis of COLO205 cells pretreated with IFN-gamma demonst rated that the IL-6R alpha chain was downregulated. These results suggest t hat, in certain colon carcinoma cells, tumor-derived IL-10 production is di rectly regulated by systemic or local production of pro-inflammatory cytoki nes, such as IL-6 and IFN-gamma.