Inflammatory bowel disease: study of cell mediated cytotoxicity for isolated human colonic epithelial cells

A better understanding of the mechanism(s) of cell mediated toxicity for colon cells in vitro may help clarify the pathogenesis of inflammatory bowel disease (IBD). We have examined both the cytotoxicity of IBD peripheral blood mononuclear cells and the kinetics of induction of such toxicity by soluble plasma factors. Peripheral blood mononuclear cells from IBD patients were found to be cytotoxic for the colon cells. With the use of Chang cells, this cytotoxicity was shown not to be due to an increase in spontaneous cell mediated cytotoxicity. Colon cell toxicity in vitro did not correlate with site of disease or severity, but decreased toxicity appeared to be associated with in vivo steroid administration. Plasma from some IBD patients was capable of inducing normal peripheral blood mononuclear cells to be toxic to colon cells. This ability was not affected by steroid therapy. The induction capacity of IBD plasma was not associated with the presence of circulating immune complexes, as measured by Raji RIA, suggesting that large complement fixing complexes are not the inducing and directing factors. Unlike findings in other systems, induction could be demonstrated after a one hour preincubation of mononuclear cells with IBD plasma. The kinetics of induction are consistent with the hypothesis that either cytophilic antibody or small circulating immune complexes arm K cells for specific colon cell lysis.