COLON-CARCINOMA CELL-LINES STIMULATE MONOCYTES AND LAMINA PROPRIA MONONUCLEAR-CELLS TO PRODUCE IL-10

Cytokines released from tumour cells may have function as signals to n eighbouring immune and inflammatory cells. Several studies have shown that the immunoregulatory cytokines IL-10 and transforming growth fact or-beta1 (TGF-beta 1) as well as prostaglandin-E-2 (PGE(2)) play an im portant role in tumour-induced immunosuppression. The aim of the study was to investigate the effect of colon carcinoma cell lines on IL-10 production in peripheral monocytes (PBMC) and lamina propria mononucle ar cells (LPMC). We examined four colon carcinoma cell lines (HT-29, C aco-2, Cola-320 and HCT-116) and determined their production of TGF-be ta 1, IL-10 and PGE(2). Peripheral monocytes were isolated by density gradient centrifugation and LPMC were isolated from surgical specimens using a collagenase digestion method. Monocytes and LPMC were culture d with colon carcinoma cell conditioned medium or in co-culture with c olon carcinoma cells. Supernatants were then determined for the produc tion of IL-10 by ELISA assays. AU colon carcinoma cell lines stimulate d peripheral monocytes as well as LPMC to produce markedly increased l evels of IL-10. Colon cancer cells secreted negligible levels of IL-10 , but high amounts of TGF-beta 1 and PGE(2). Neutralization of TGF-bet a 1 by administration of anti-TGF-beta as well as neutralization of PG E(2) with anti-PGE(2) antisera reduced the IL-10 production of monocyt es markedly, indicating that tumour cell-derived TGF-beta 1 and PGE(2) are major factors for IL-10 stimulation, In vitro stimulation of mono cytes with TGF-beta 1 and PGE(2) could confirm that TGF-beta 1 as well as PGE(2) at picogram concentrations were able to prime monocytes for enhanced IL-IO production. Our results demonstrate that colon carcino ma fell lines enhance the ability of monocytes and intestinal macropha ges to produce IL-10. The stimulation of monocyte IL-10 by colon cance r cell-derived TGF-beta 1 and PGE(2) may act as a tumour-protecting me chanism by impairing the activation of anti-tumour cytokines.