ABSENCE OF MODULATING EFFECTS OF CYTOKINES ON ANTIOXIDANT ENZYMES IN PERITONEAL MESOTHELIAL CELLS

Objective: To investigate the modulation of superoxide dismutase, glut athione peroxidase, and catalase by cytokines and endotoxin in human p eritoneal mesothelial cells. Design: Cultured human peritoneal mesothe lial cells were treated with various concentrations of interleukin-1 a lpha, tumor necrosis factor-alpha(TNF alpha), interleukin-6, interleuk in-8, transforming growth factor-beta (TGF beta), and lipopolysacchari de. Cell morphology was observed and the activities of superoxide dism utase, catalase, and glutathione peroxidase were assayed. The antioxid ant enzyme activities of human peritoneal mesothelial cells were also compared with those of human liver and kidney tissues. Results: Interl eukin-1 alpha, TNF alpha, TGF beta, and lipopolysaccharide caused dose -dependent cytotoxicities in mesothelial cells. The activities of thes e three antioxidant enzymes did not change after treatment with cytoki nes and endotoxin. The total superoxide dismutase activity of confluen t human peritoneal mesothelial cells was found to be greater than that of human liver and kidney tissues and was composed mostly of manganes e superoxide dismutase activity. Furthermore, glutathione peroxidase a nd catalase activities of human peritoneal mesothelial cells were lowe r than those of human liver and kidney tissues. Conclusion: In human p eritoneal mesothelial cells, lack of induction of antioxidant enzymes by inflammatory cytokines, as well as high superoxide dismutase activi ty accompanied by insufficient glutathione peroxidase and catalase act ivities may both contribute to the susceptibility of these cells to ox idative damage. Therefore, appropriate management to decrease oxidativ e injury to the peritoneum should be taken into consideration when tre ating long-term continuous ambulatory peritoneal dialysis patients.