Type I Interferon controls the onset and severity of autoimmune manifestations in lpr mice

J Autoimmun. 2003 Feb;20(1):15-25. doi: 10.1016/s0896-8411(02)00109-9.


Type I Interferons (IFN-I) are immunoregulatory cytokines that enhance activation and survival of many cellular components of the immune system. In the present work, we evaluated the effect of IFN-I on the development of the lymphoproliferative disorder in Fas-defective lpr mice. We report that sustained injection of polyinosinic:polycytidylic acid, a potent inducer of IFN-I, in B6 lpr mice resulted in a dramatic aggravation of the renal disease, higher titers of autoantibodies, a 10-fold increase in serum Ig and accumulation of activated lymphocytes. Moreover, introducing a null mutation for the IFN-I-Receptor gene into the lpr background resulted in dramatic decrease of immune complexes deposition in the kidney and reduced lymphadenopathy. While several recent reports correlated serum levels of IFN-alpha with disease activity in systemic Lupus erythematosus patients, our findings establish a causal link from IFN-I production to the onset and severity of another related autoimmune syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / metabolism*
  • Disease Models, Animal
  • Female
  • Glomerulonephritis / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Interferon Inducers / pharmacology
  • Interferon Type I / drug effects
  • Interferon Type I / metabolism*
  • Lupus Erythematosus, Systemic / metabolism
  • Mice
  • Mice, Inbred MRL lpr
  • Poly I-C / pharmacology


  • Immunoglobulin G
  • Immunoglobulin M
  • Interferon Inducers
  • Interferon Type I
  • Poly I-C