Monoclonal anti-tumor necrosis factor antibody renders non-obese diabetic mice hypersensitive to irradiation and enhances insulitis development

In attempt to evaluate biological roles of tumor necrosis factor (TNF), we studied the effects of anti-TNF mAb in non-obese diabetic (NOD) mice. Anti-murine TNF mAb rendered NOD mice hypersensitive to the lethal effects of radiation and prevented the reconstitution of lethally Irradiated mice with adoptively transferred lymphocytes. While TNF-α reduced the incidence of diabetes development in the adoptive transfer system even when given 6 days post-transfer, mAb to TNF could not reduce or increase the incidence of diabetes compared to control mice. Administration of TNF-α for 4 or 8 weeks significantly reduced the Incidence of spontaneous Insulitis in NOD mice, while antl-TNF mAb given for 8 weeks Increased the Incidence of insulltls significantly.