Interferon-α as a Mediator of Polyinosinic:Polycytidylic Acid–Induced Type 1 Diabetes

  1. Devasenan Devendra,
  2. Jean Jasinski,
  3. Evie Melanitou,
  4. Maki Nakayama,
  5. Marcella Li,
  6. Brooke Hensley,
  7. Johanna Paronen,
  8. Hiroaki Moriyama,
  9. Dongmei Miao,
  10. George S. Eisenbarth and
  11. Edwin Liu
  1. From the Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado
  1. Address correspondence and reprint requests to Dr. Edwin Liu, MD, Barbara Davis Center for Childhood Diabetes, 4200 East 9th Ave., Box B140, University of Colorado Health Sciences Center, Denver, CO 80262. E-mail: edwin.liu{at}uchsc.edu

Abstract

A number of studies and clinical case reports have implicated interferon (IFN)-α as a potential mediator of type 1 diabetes pathogenesis. Administration of polyinosinic:polycytidylic acid (poly I:C), a mimic of viral double-stranded RNA, induces diabetes in C57BL/6 mice expressing the B7.1 costimulatory molecule in islets. We investigated the potential role of IFN-α in this disease model. The quantitative correlation between IFN-α levels and time to diabetes, diabetes prevention with anti–IFN-α antibody, and ability of IFN-α itself to induce diabetes are consistent with the hypothesis that poly I:C in this model acts by induction of IFN-α in a genetically susceptible host. Numerous recent studies highlight the importance of the innate immune system and toll receptors in determining adaptive immune responses, and we speculate that for type 1 diabetes, viral and other environmental factors may act through induction of IFNs.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted May 3, 2005.
    • Received January 3, 2005.
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