Role of the equilibrium between colon cancer and mononuclear cells in cytokine production.

Patients with ulcerative colitis and Crohn's disease are at increased risk for colorectal cancer, a phenomenon assumed to be at least in part consequence of chronic inflammation. The purpose of this study was to examine whether human colon cancer cells may promote immune cells to produce cytokines, particularly those involved in inflammatory reaction. HT-29 and RKO human colon cancer cell lines were used. Human peripheral blood mononuclear cells (PBMC) were incubated for 24 h without or with cancer cells, or with supernatants derived from these cells cultured at the same conditions. TNFα, IL-1β, IL-6, IFNγ, IL-1ra and IL-10 secreted by PBMC were detected using specific ELISA kits. Interaction between colon cancer cells and PBMC induced secretion of pro- and anti-inflammatory cytokines in a dose-dependent manner. Furthermore, supernatants from increasing number of colon cancer cells caused a dose-dependent cytokine secretion. However, the production of cytokines was more pronounced when PBMC were directly exposed to tumor cells as compared to their supernatants. The results of our experimental model demonstrating an altered balance between pro- and anti-inflammatory cytokines generated by interaction between colon cancer and immune cells support the role of the malignant cells in promoting inflammation as one of the mechanisms for progression of colon cancer.