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. |