TY - JOUR
T1 - IFN-α induces early lethal lupus in preautoimmune (New Zealand Black x New Zealand White)F1 but not in BALB/c mice
AU - Mathian, Alexis
AU - Weinberg, Arthur
AU - Gallegos, Mike
AU - Banchereau, Jacques
AU - Koutouzov, Sophie
PY - 2005/3/1
Y1 - 2005/3/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.174.5.2499
DO - 10.4049/jimmunol.174.5.2499
M3 - Article
C2 - 15728455
AN - SCOPUS:14044278824
SN - 0022-1767
VL - 174
SP - 2499
EP - 2506
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -