Gamma interferon paradoxically inhibits the development of diabetes in the NOD mouse

J Autoimmun. 2002 Nov;19(3):129-37. doi: 10.1006/jaut.2002.0604.


Gamma interferon (IFN-gamma) has been thought to play an important role in the pathogenesis of diabetes. This report determines if rIFN-gamma administration to NOD mice paradoxically inhibits the development of diabetes. Injections of recombinant rIFN-gamma of 5 x 10(3), 20 x 10(3), and 100 x 10(3) units, dose dependently inhibited the development of diabetes. The maximal rIFN-gamma dose decreased the incidence of diabetes from 74% in control animals to 42%. 100x10(3) unit rIFN-gamma dose significantly decreased insulitis score, and increased islet number. The development of diabetes in irradiated NOD mice was slower in animals injected with spleen cells from rIFN-gamma treated than from saline treated NOD mice suggesting that rIFN-gamma decreases anti-islet effector cell activity. The susceptibility to apoptosis was increased in splenic cells of rIFN-gamma treated mice. The expressions of the co-stimulatory molecules B7-2 and ICAM-1 were significantly increased in spleen cells of rIFN-gamma treated mice while the expression of MHC class I was decreased. In vitro studies demonstrated that NOD mouse mononuclear spleen cells preincubated with rIFN-gamma and subsequently cocultured with responder cells, potently inhibited responder T-cell proliferative responses. rIFN-gamma administration decreased IL-12 and IL-2 mRNA expression in spleen cells while increasing IL-1 expression. In conclusion, rIFN-gamma inhibits the diabetic process in NOD mice by decreasing anti-islet effector activity and in turn decreasing insulitis and islet destruction. The suppression of Th1 cell related cytokines and/or augmentation of the macrophage cytokine IL-1 may play a role in the diabetes sparing effect of rIFN-gamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cytokines / drug effects
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / prevention & control*
  • Female
  • Genes, MHC Class I
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / pharmacology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / immunology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred NOD
  • Spleen / metabolism
  • T-Lymphocytes / drug effects


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • Cell Adhesion Molecules
  • Cytokines
  • Membrane Glycoproteins
  • Interferon-gamma