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

Recent studies indicate that IFN-alpha is involved in pathogenesis of systemic lupus erythematosus. However, direct proof that IFN-alpha 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-alpha results in preautoimmune (New Zealand Black (NZB) X New Zealand White (NZW))F-1, 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-alpha treatment. Proteinuria and death caused by glomerulonephritis occurred in all treated mice within, respectively, similar to9 and similar to18 wk, at a time when all untreated (NZB X NZW)F-1 did not show any sign of disease. IFN-alpha 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-alpha were dose dependent. (NZB X NZW)F-1 infused with purified murine IFN-alpha also showed acceleration of lupus. Thus, prolonged expression of IFN-alpha in vivo induces early lethal lupus in susceptible animals.