Interferon-gamma is required for lupus nephritis in mice treated with the hydrocarbon oil pristane

Background. Although the precise mechanisms leading to lupus nephritis rema in obscure, both T(H)1 and T(H)2 cytokines have been implicated. The presen t study examined the roles of interleukin (IL)-4 and interferon-gamma (IFN- gamma) in a novel inducible form of lupus that develops in non-autoimmune m ice treated with the hydrocarbon oil pristane. Methods. BALB/c IL-4 or IFN-gamma deficient mice (IL-4 -/-, IFN gamma -/-) and wild type controls (+/+) received either pristane or phosphate-buffered saline (PBS) IP. Serial sera were analyzed for anti-DNA/chromatin, anti-RN P/Sm, and total immunoglobulin levels. Proteinuria was measured and kidneys were examined by direct immunofluorescence and light microscopy. Results. Renal disease did not develop in pristane-treated IFN-gamma -/- mi ce, as assessed by the absence of capillary immune deposits, glomerular pat hology and proteinuria whereas IL-4 -/- mice developed renal disease simila r to +/+ mice. Production of IgG anti-single stranded DNA and anti-chromati n antibodies was abrogated in IFN-gamma -/- mice. In contrast, these autoan tibodies were produced at similar or higher frequencies and levels by IL-4 -/- versus wild-type mice. The frequency of anti-nRNP/Sm was markedly reduc ed in IFN-gamma -/- mice. IL-4 deficiency had little effect on the producti on of anti-DNA/chromatin and anti-nRNP/Sm. Conclusions. IFN-gamma is essential for the induction of nephritis and anti -DNA/chromatin following pristane exposure in BALB/c mice, suggesting that genetic or environmental factors influencing T(H)1-T(H)2 balance could be a n important determinant of renal disease in lupus.