Development of lupus in BXSB mice is independent of IL-4

Although systemic lupus erythematosus appears to be a humorally mediated di sease, both Th1 and Th2 type responses have been implicated in its pathogen esis, The Th1 response, as exemplified by IFN-gamma production, has been un iformly shown in mouse lupus models to be critical for disease induction. T he role of Th2 type responses, however, is more complicated, with some stud ies showing detrimental and others beneficial effects of IL-4 in these mode ls. To further address this issue, we generated and analyzed IL-4 gene-defi cient BXSB mice. Mice homozygous for this deletion had significantly lower serum levels of total IgG1 compared with wild-type BXSB, consistent with th e lack of IL-4, However, no significant differences were observed in mortal ity, spleen weight, severity of glomerulonephritis, levels of anti-chromati n and anti-ssDNA Abs, or frequency of activated (CD44(high)) 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 in duction and maintenance of lupus in this strain.