Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1

Proc Natl Acad Sci U S A. 1990 Feb;87(3):968-72. doi: 10.1073/pnas.87.3.968.

Abstract

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.

MeSH terms

  • Animals
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / prevention & control*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Female
  • Immunization, Passive
  • Interleukin-1 / therapeutic use*
  • Islets of Langerhans / pathology*
  • Lymphocytes / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Recombinant Proteins / therapeutic use*
  • Tumor Necrosis Factor-alpha / therapeutic use*

Substances

  • Interleukin-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha