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

Although the precise mechanisms leading to lupus nephritis remain obscure, both T_H1 and T_H2 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.

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.

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.

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 T_H1-T_H2 balance could be an important determinant of renal disease in lupus.