IFN-α induces early lethal lupus in preautoimmune (New Zealand Black x New Zealand White)F1 but not in BALB/c mice

Alexis Mathian, Arthur Weinberg, Mike Gallegos, Jacques Banchereau, Sophie Koutouzov

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205 Scopus citations

Abstract

Recent studies indicate that IFN-α is involved in pathogenesis of systemic lupus erythematosus. However, direct proof that IFN-α is not only necessary, but also sufficient to induce lupus patfaogenicity is lacking. In this study, we show that in vivo adenovector-mediated delivery of marine IFN-α results in preautoimmune (New Zealand Black (NZB) x New Zealand White (NZW))F1, but not in normal, mice, in a rapid and severe disease with all characteristics of systemic lupus erythematosus. Anti-dsDNA Abs appeared as soon as day 10 after initiation of IFN-α treatment. Proteinuria and death caused by glomerulonephritis occurred in all treated mice within, respectively, ∼9 and ∼18 wk, at a time when all untreated (NZB X NZW)F1 did not show any sign of disease. IFN-α in vivo induced an overexpression of B lymphocyte stimulator in circulation at similar levels in both the preautoimmune and the normal mouse strains. All effects elicited by IFN-α were dose dependent. (NZB X NZW)F1 infused with purified murine IFN-α also showed acceleration of lupus. Thus, prolonged expression of IFN-α in vivo induces early lethal lupus in susceptible animals.

Original languageEnglish (US)
Pages (from-to)2499-2506
Number of pages8
JournalJournal of Immunology
Volume174
Issue number5
StatePublished - Mar 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Mathian, A., Weinberg, A., Gallegos, M., Banchereau, J., & Koutouzov, S. (2005). IFN-α induces early lethal lupus in preautoimmune (New Zealand Black x New Zealand White)F1 but not in BALB/c mice. Journal of Immunology, 174(5), 2499-2506.