Failure of exogenously administered interferon-γ or blockage of endogenous interleukin-4 with specific inhibitors to augment the incidence of autoimmune diabetes in male NOD mice

Ming Xiang, Paola Zaccone, Roberto Di Marco, Robert Harris, Gaetano Magro, Maurizio Di Mauro, Pier Luigi Meroni, Gianni Garotta, Ferdinando Nicoletti

Research output: Contribution to journalArticlepeer-review

Abstract

Interferon (IFN)-γ and interleukin (IL)-4 are prototypic type 1 and type 2 cytokines which are known to play pathogenetic and protective roles, respectively, in NOD mouse IDDM. The capacity of male NOD mice to produce more IL-4 and less IFN-γ within the insulitic lesions than females has been suggested to contribute to their lower incidence of diabetes. In this study we have tested the effects of prolonged prophylactic treatment of male NOD mice with rat IFN-γ, mouse IFN-γ, anti-IL-4 monoclonal antibody (mAb) and recombinant murine soluble IL-4 receptor (smIL-4R) on the diabetogenic events leading to insulitis and diabetes. None of these treatments influenced spontaneous and/or cyclophosphamide-induced autoimmune diabetogenesis in male NOD mice. Control mice exhibited comparable histological signs of insulitis and incidence of diabetes to those treated with either mouse/rat IFN-γ or specific IL-4 inhibitors. On the contrary, both clinical and histological signs of diabetes were suppressed by prophylactic treatment with anti-IFN-γ mAb. These findings indicate that the autoimmune diathesis of male NOD mice towards IDDM cannot be augmented by manipulation of endogenous IFN-γ or IL-4.

Original languageEnglish
Pages (from-to)71-80
Number of pages10
JournalAutoimmunity
Volume30
Issue number2
Publication statusPublished - 1999

Keywords

  • Diabetes
  • Immunotherapy
  • Interferon-γ
  • Interleukin-4
  • NOD mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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