期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2009
卷号:106
期号:13
页码:5294-5299
DOI:10.1073/pnas.0900615106
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:A major involvement of IFN{alpha} in the etiopathogenesis of systemic lupus erythematosus has been suggested by clinical observations, including the increase of serum levels of this cytokine in patients with active disease. Supporting this hypothesis, we have shown that expression of IFN{alpha} from a recombinant adenovirus (IFN{alpha} Adv) precipitates lupus manifestations in genetically susceptible New Zealand Black (NZB) x New Zealand White (NZW)F1 mice (NZB/W) but not in BALB/c mice. In the present investigation, we have prepared an IFN{alpha} immunogen, termed IFN{alpha} kinoid, which, appropriately adjuvanted, induces transient neutralizing antibodies (Abs) but no cellular immune response to the cytokine and without apparent side effects. Using this preparation, we also showed that, in kinoid-vaccinated NZB/W mice, lupus manifestations, including proteinuria, histological renal lesions, and death triggered by IFN{alpha} Adv challenge were delayed/prevented as long as an effective threshold of anti-IFN{alpha} inhibitory capacity was present in the serum.