IMPAIRED INTERLEUKIN-2 PRODUCTION IN ACTIVE ULCERATIVE-COLITIS IS REVERSED BG CALCIUM IONOPHORE PLUS PHORBOL-MYRISTATE ACETATE AND RELATED TO ALTERED INTRACELLULAR CA2+ RESPONSES

Phytohemagglutin in (PHA)-induced IL-2 production in vitro by peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) from patients with active UC (n=24, n=8, respectively) was significantly less than that in controls (n=13, n=8, respectively) and inactive patients (n=11). In contrast, PBMC from inactive disease showed no significant difference when compared with the controls. Depressed IL-2 production in active UC was not reversed by the addition of anti-CD3 monoclonal antibody plus phorbol myristate acetate (PMA), but was largely reversed by adding calcium ionophore plus PMA. Using a fluorescent Ca2+ probe fura-2, we found that after PHA stimulation LPMC from patients with active UC showed a lower magnitude of rise in intracellular free calcium concentration ([Ca2+](i)) than control cells. These results suggest that impaired PHA-induced IL-2 production in active UC may be related to some alterations of the early signaling events that cause elevation of the [Ca2+](i).