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

Abstract

Background. Although the precise mechanisms leading to lupus nephritis remain obscure, both TH1 and TH2 cytokines have been implicated. The present study examined the roles of interleukin (IL)-4 and interferon-γ (IFN-γ) in a novel inducible form of lupus that develops in non-autoimmune mice treated with the hydrocarbon oil pristane. Methods. BALB/c IL-4 or IFN-γ deficient mice (IL-4 -/-, IFNγ -/-) and wild type controls (-/-) received either pristane or phosphate-buffered saline (PBS) IP. Serial sera were analyzed for anti-DNA/chromatin, anti-RNP/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-γ -/- mice, as assessed by the absence of capillary immune deposits, glomerular pathology and proteinuria whereas IL-4 -/- mice developed renal disease similar to -/- mice. Production of IgG anti-single stranded DNA and anti-chromatin antibodies was abrogated in IFN-γ -/- mice. In contrast, these autoantibodies were produced at similar or higher frequencies and levels by IL-4 -/- versus wild-type mice. The frequency of anti-nRNP/Sm was markedly reduced in IFN-γ -/- mice. IL-4 deficiency had little effect on the production of anti-DNA/chromatin and anti-nRNP/Sm. Conclusions. IFN-γ 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 TH1-TH2 balance could be an important determinant of renal disease in lupus.