Local and systemic liberation of proinflammatory cytokines in ulcerative colitis

Abstract

Determination of plasma and tissue cytokine levels in inflammatory bowel disease have frequently resulted in conflicting data. In the present study we determined in patients with ulcerative colitis (UC), the levels of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma, and tumor-necrosis factor (TNF)-alpha liberated by peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) after 48-hr culture with pokeweed mitogen (PWM). IL-1beta, IL-6, IFN-gamma and TNF-alpha in the supernatant were detected by ELISA. Results show low basal levels of IL-1beta secretion by PBMC and LPMC, and a considerable increase after mitogen stimulation. Basal IL-6 production by PBMC was higher in UC patients than in controls [2029 pg/ml, CI95(-165 to 4223) vs 572 pg/ml (-383 to 1527) respectively, P = 0.05] and also after PWM activation [14,995 pg/ml (7759-22,230) vs 6598 pg/ml (3240-9956), respectively, P = 0.05]. In LPMC, no differences in IL-6 secretion were observed. TNF-alpha in activated PBMC of patients with UC was not significantly increased in relation to control (P = 0.09). No constitutive secretion of IFN-gamma was observed in mononuclear cells. IFN-gamma levels secreted by activated LPMC were lower in patients with UC than in controls [1571 pg/ml (-108 to 3251) vs 7953 pg/ml (3851-12,055), respectively, P = 0.03]. These results suggest that IL-6, IL-1beta, and TNF-alpha participate as mediators in the inflammatory phenomena observed in UC. Further studies are necessary to evaluate the role of IFN-gamma in this condition.