Up-regulation of the IL-1-IL-6 network stimulates systemic expression of C-reactive protein (CRP). This cytokine network system plays a pivotal role in inducing angiogenic growth factors in intestinal mucosa. Serum CRP level and tissue concentrations of cytokines in colorectal cancer patients were determined and an in vitro model was employed to determine the time course of induction of IL-6 in Caco-2 cells. Increased serum CRP was associated with recurrent disease and shorter survival time. Intense surgical stress and the presence of an acute phase reactant were independently associated with overexpression of IL-6 in the tumor. Enhanced IL-6 protein expression in Caco-2 cells induced by the initial treatment with IL-1beta or lipopolysaccharide could be abrogated by additional presupplementation of IL-1ra. The presence of an acute phase reactant reflects uncontrolled up-regulation of the local IL-1-IL-6 network system in the tumor, which may enhance the survival and proliferation of remnant cancer cells after tumor resection.