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IFN-α Induces Early Lethal Lupus in Preautoimmune (New Zealand Black × New Zealand White)F1 but Not in BALB/c Mice

2005; American Association of Immunologists; Volume: 174; Issue: 5 Linguagem: Inglês

10.4049/jimmunol.174.5.2499

1550-6606

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

Monoclonal and Polyclonal Antibodies Research

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 pathogenicity is lacking. In this study, we show that in vivo adenovector-mediated delivery of murine IFN-α results in preautoimmune (New Zealand Black (NZB) × 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 × 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 × 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.