IFN-alpha 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, approximately 9 and approximately 18 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.
Mathian
Alexis
A
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
Weinberg
Arthur
A
Gallegos
Mike
M
Banchereau
Jacques
J
Koutouzov
Sophie
S
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D053264:B-Cell Activating Factor; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000401:mortality; D007074:Immunoglobulin G / Q000096:biosynthesis; D007275:Injections, Intravenous; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000302:isolation & purification; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000401:mortality*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology
D000974:Antibodies, Antinuclear; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D016898:Interferon-alpha; D008565:Membrane Proteins; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D004247:DNA