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Publication : Roles of IL-4 and IL-12 in the development of lupus in NZB/W F1 mice.

First Author  Nakajima A Year  1997
Journal  J Immunol Volume  158
Issue  3 Pages  1466-72
PubMed ID  9013993 Mgi Jnum  J:38365
Mgi Id  MGI:85736 Doi  10.4049/jimmunol.158.3.1466
Citation  Nakajima A, et al. (1997) Roles of IL-4 and IL-12 in the development of lupus in NZB/W F1 mice. J Immunol 158(3):1466-72
abstractText  Development of either Th1 or Th2 cell subsets has profound immunologic consequences, either pathogenic or protective, in several autoimmune diseases. However, it remains unclear which subset of Th cells plays a more critical role in lupus. In this study, we examined IL-4 and IL-12, which play decisive roles in the development of Th2 and Th1, respectively, in the IgG autoantibody production and development of lupus nephritis in NZB/W (B/W) F1 mice. Transfer of either IL-4- or IL-12-stimulated splenocytes from 5-mo-old B/W F1 mice into B/W F1 mice of the same age enhanced the production of IgG anti-dsDNA Ab. Consistently, administration of mAb against either IL-4 or IL-12 before the onset of lupus could inhibit the production of IgG anti-dsDNA Ab. However, only anti-IL-4 mAb was effective in preventing the onset of lupus nephritis. This discrepancy appeared to be explained by the differential effect on the production of IgG3-type autoantibody and TNF production. Interestingly, when combined, anti-IL-12 mAb abrogated the beneficial effect of anti-IL-4 mAb. These results indicate that both Th2 and Th1 contribute to the IgG autoantibody production, and IL-4 and IL-12 play key roles in the complexity of cytokine regulation in the pathogenesis of autoimmunity in lupus, but the former is more critical.
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