Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): Similarities between TNF-α and interleukin

Chaim O. Jacob, Sadakazu Aiso, Sara A. Michie, Hugh O. Mcdevitt, Hans Acha-Orbea

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

The role of tumor necrosis factor α (TNF-α) in the pathogenesis of autoimmune diabetes mellitus was tested in the nonobese mouse (NOD) model system. The effects of TNF-α 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-α. Treatment with TNF-α caused a significant reduction in the lymphocytic infiltration associated with the destruction of the insulin-producing beta cells. Class II major histocompatibility complex la expression by islet cells was not up-regulated by TNF-α. Moreover, TNF-α 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-α were shared by interleukin 1α in this system. These studies have implications for the pathogenesis and therapy of autoimmune diabetes mellitus.

Original languageEnglish
Pages (from-to)968-972
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number3
Publication statusPublished - 1990
Externally publishedYes

Fingerprint

Inbred NOD Mouse
Interleukins
Tumor Necrosis Factor-alpha
Diabetes Mellitus
Adoptive Transfer
Type 1 Diabetes Mellitus
Lymphocytes
Major Histocompatibility Complex
Interleukin-1
Islets of Langerhans
Therapeutics
Insulin

Keywords

  • Adoptive transfer
  • Autoimmune disease
  • Ia expression
  • Insulitis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF) : Similarities between TNF-α and interleukin. / Jacob, Chaim O.; Aiso, Sadakazu; Michie, Sara A.; Mcdevitt, Hugh O.; Acha-Orbea, Hans.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 3, 1990, p. 968-972.

Research output: Contribution to journalArticle

Jacob, Chaim O. ; Aiso, Sadakazu ; Michie, Sara A. ; Mcdevitt, Hugh O. ; Acha-Orbea, Hans. / Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF) : Similarities between TNF-α and interleukin. In: Proceedings of the National Academy of Sciences of the United States of America. 1990 ; Vol. 87, No. 3. pp. 968-972.
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