Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1.
The role of tumor necrosis factor alpha (TNF-alpha) in the pathogenesis of autoimmune diabetes mellitus was tested in the nonobese mouse (NOD) model system. The effects of TNF-alpha were assessed on three levels: (i) insulitis development, (ii) development of overt diabetes, (iii) adoptive transfer of diabetes by splenic lymphocytes. Spontaneous diabetes mellitus was blocked in NOD mice by long-term treatment with recombinant TNF-alpha. Treatment with TNF-alpha caused a significant reduction in the lymphocytic infiltration associated with the destruction of the insulin-producing beta cells. Class II major histocompatibility complex Ia expression by islet cells was not up-regulated by TNF-alpha. Moreover, TNF-alpha was able to suppress the induction of diabetes in adoptive transfer of lymphocytes from diabetic female mice to young nondiabetic male NOD mice. These activities of TNF-alpha were shared by interleukin 1 alpha in this system. These studies have implications for the pathogenesis and therapy of autoimmune diabetes mellitus.
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305.
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Jacob
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Aiso
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Michie
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McDevitt
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Acha-Orbea
D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007116:Immunization, Passive; D007375:Interleukin-1 / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000473:pathology*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011994:Recombinant Proteins / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha