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

A Mathian, A Weinberg, M Gallegos… - The Journal of …, 2005 - journals.aai.org
A Mathian, A Weinberg, M Gallegos, J Banchereau, S Koutouzov
The Journal of Immunology, 2005journals.aai.org
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)) 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 …
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)) 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-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) F 1 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) F 1 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.
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