ADVANCED COLORECTAL-CANCER IS ASSOCIATED WITH IMPAIRED INTERLEUKIN-12AND ENHANCED INTERLEUKIN-10 PRODUCTION

Interleukin 12 (IL-12) is a heterodimeric cytokine that has been demon strated to have a major role in stimulating a cell-mediated antitumor response. IL-10, a product of T helper 2 lymphocytes, is its most pote nt inhibitor. The aim of this study was to investigate whether patient s with colorectal cancer had an imbalance in production of IL-12 and I L-10 preoperatively, and whether this was associated with advanced dis ease at surgery. Blood was obtained before surgery from 60 patients wi th colorectal cancer and from 30 controls. Peripheral blood mononuclea r cells were incubated with Staphylococcus aureus Cowan's strain 1 in vitro for 24 h to assess IL-12 expression after stimulation, and serum was used for IL-10 measurement. IL-12 and IL-10 levels were assessed by ELISA, A single pathologist staged the tumors according to the tumo r-node-metastasis (TNM) and Dukes' classifications. Patients with colo rectal cancer had significantly lower levels of IL-12 (P < 0.001) and higher levels of IL-10 (P = 0.004) compared to controls, In addition, lower levels of IL-12 were detected in those patients who were node po sitive (P < 0.05), had Dukes' C lesions (P less than or equal to 0.001 ), and T-3 or T-4 lesions (P < 0.033) when compared to controls. Patie nts with Dukes' B and C lesions (P < 0.01) and T-3 and T-4 lesions (P < 0.05) also had higher levels of IL-10 compared to controls, This stu dy is the first to demonstrate that patients,vith colorectal cancer ha ve decreased IL-12 production and increased serum IL-IO, This suggests an impaired T helper 1 cell-mediated antitumor response and provides some justification for exogenous IL-12 therapy or anti-IL-10 therapy i n these patients.