Development of Lupus in BXSB Mice Is Independent of IL-4

Although systemic lupus erythematosus appears to be a humorally mediated disease, both Th1 and Th2 type responses have been implicated in its pathogenesis. The Th1 response, as exemplified by IFN-gamma production, has been uniformly shown in mouse lupus models to be critical for disease induction. The role of Th2 type responses, however, is more complicated, with some studies showing detrimental and others beneficial effects of IL-4 in these models. To further address this issue, we generated and analyzed IL-4 gene-deficient BXSB mice. Mice homozygous for this deletion had significantly lower serum levels of total IgG1 compared with wild-type BXSB, consistent with the lack of IL-4. However, no significant differences were observed in mortality, spleen weight, severity of glomerulonephritis, levels of anti-chromatin and anti-ssDNA Abs, or frequency of activated (CD44high) CD4+ T cells. The anti-chromatin Ab isotype response was virtually all Th1 type in both the knockout and wild-type BXSB. These findings directly demonstrate that IL-4 and, by inference, Th2 cells are not obligatory participants in the induction and maintenance of lupus in this strain.