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

Int J Oncol. 2001 Mar;18(3):581-6.


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-alpha, IL-1 beta, IL-6, IL-8, and IFN-gamma 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-alpha, IL-1 beta or IFN-gamma. 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-gamma dose-dependently inhibited 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 that high dose IFN-gamma (>100 ng/ml) significantly inhibited their proliferation. Northern analysis of COLO205 cells pretreated with IFN-gamma demonstrated that the IL-6R alpha 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-gamma.

MeSH terms

  • Blotting, Northern
  • Cell Division / drug effects
  • Colonic Neoplasms / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interferon-gamma / pharmacology*
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / genetics
  • Interleukin-6 / pharmacology*
  • RNA, Messenger / biosynthesis
  • Tumor Cells, Cultured / drug effects*
  • Tumor Cells, Cultured / metabolism


  • Interleukin-6
  • RNA, Messenger
  • Interleukin-10
  • Interferon-gamma