IL-10 has been shown to play a crucial role in immunosuppression in cancer patients. We explored the regulation of IL-10 production by TNF-α, IL-1β, IL-6, IL-8, and IFN-γ in human colon carcinoma COLO205 cells. Northern analysis revealed a marked expression of IL-10 mRNA after stimulation by IL-6, and a marginal but significant expression by TNF-α, IL-1β or IFN-γ. No IL-10 mRNA expression was observed when cells were untreated or incubated with IL-8. IL-10 in the culture supernatants showed good agreement with mRNA expression. In addition, IFN-γ dose-dependently inhibited this IL-6-induced production of IL-10. MTT assay revealed that low dose IFN-γ (1-10 ng/ml) had no effect on growth of COLO205 cells, but that high dose IFN-γ (>100 ng/ml) significantly inhibited their proliferation. Northern analysis of COLO205 cells pretreated with IFN-γ demonstrated that the IL-6Rα chain was down-regulated. These results suggest that, in certain colon carcinoma cells, tumor-derived IL-10 production is directly regulated by systemic or local production of pro-inflammatory cytokines, such as IL-6 and IFN-γ.

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