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-alpha 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-alpha for 4 or 8 weeks significantly reduced the incidence of spontaneous insulitis in NOD mice, while anti-TNF mAb given for 8 weeks increased the incidence of insulitis significantly.
Jacob
C O
CO
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305.
Aiso
S
S
Schreiber
R D
RD
McDevitt
H O
HO
D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011836:Radiation Tolerance / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha