Lise Wogensen

Postnatal anti-interferon-gamma treatment prevents pancreatic inflammation in transgenic mice with beta-cell expression of interferon-gamma

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • L Wogensen
  • L Molony, Danmark
  • D Gu
  • ,
  • T Krahl, Danmark
  • S Zhu
  • ,
  • N Sarvetnick

beta-Cell-targeted expression of interferon-gamma (IFN-gamma) leads to pancreatitis and immune sensitization to beta-cells. This transgenic model is used to explore the possible role of locally produced IFN-gamma in loss of tolerance to beta-cell-specific antigens in insulin-dependent diabetes mellitus (IDDM). The aim of the present study was to test if postnatal treatment with antibodies against IFN-gamma could inhibit morphological changes in the IFN-gamma transgenic pancreas, even though the transgene is expressed during embryogenesis. Treatment with a monoclonal rat anti-mouse IFN-gamma antibody for 6 weeks, starting from 5 to 7 days of age, completely inhibited IFN-gamma-induced morphological changes in the pancreas, and only a modest inflammatory reaction emerged after prolonged treatment for 12 weeks. The lack of morphological changes may reflect the ability of nonterminally differentiated neonatal pancreatic cells to compensate for transgene-induced pathological alterations occurring in utero prior to the antibody treatment. We conclude that inflammation and altered pancreas morphology in the transgenic mice is the result of the biological actions of IFN-gamma and not by disrupted islet development due to transgene overexpression in the pancreatic beta-cells. Furthermore, our treatment schedule can serve as a model for future intervention studies in the transgenic mice, elaborating the role of IFN-gamma in localized inflammatory reactions, IDDM in particular.

OriginalsprogEngelsk
TidsskriftJournal of interferon research
Vol/bind14
Nummer3
Sider (fra-til)111-6
Antal sider6
ISSN0197-8357
StatusUdgivet - jun. 1994

Se relationer på Aarhus Universitet Citationsformater

ID: 95608944