Tumor necrosis factor and interferon-gamma augment anticolon antibody-dependent cellular cytotoxicity in ulcerative colitis

The effect of tumor necrosis factor (TNF) and interferon (IFN)-gamma on antibody-dependent cellular cytotoxicity (ADCC) in patients with ulcerative colitis (UC) was investigated. ADCC activity was measured by the Cr-51 release assay, using peripheral blood mononuclear cells of healthy subjects as effector cells and RPMI4788 cells derived from human colon cancer as target cells. ADCC activity under sera from healty subjects remained low whether or not the effector cells were pretreated with TNF (100 U/ml, 16h). Under sera from UC patients, ADCC activity of 13.9%, compared to 9.6% when pretreatment was deleted. The effect of IFN pretreatment (100 U/ml, 16h) was also examined under sera from UC patients; in that experiment activity rose to 26.8%, in comparison to a 10.7% when IFN-gamma pretreatment was deleted. Finally, when the effector cells were pretreated with both TNF and IFN-gamma (100 U/ml of each, 16h) the ADCC activity under sera from UC patients was higher than when either TNF or IFN-gamma were used alone. These results suggest that TNF and IFN-gamma, by increasing ADCC activity in UC lesions, are involved in cell injury in the colonic epithelium. IFN-gamma appears to increase ADCC activity by increasing the number of high affinity monocyte Fc gamma RI receptors, while TNF increases ADCC activity by a different mechanism.