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

Kidney Int. 2001 Dec;60(6):2173-80. doi: 10.1046/j.1523-1755.2001.00045.x.


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-gamma (IFN-gamma) 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-gamma deficient mice (IL-4 -/-, IFNgamma -/-) 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-gamma -/- 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-gamma -/- 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-gamma -/- mice. IL-4 deficiency had little effect on the production 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 TH1-TH2 balance could be an important determinant of renal disease in lupus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / immunology
  • Antibody Formation
  • Autoantibodies / immunology
  • Immunoglobulin G / biosynthesis
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Lupus Nephritis / chemically induced*
  • Lupus Nephritis / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout / genetics
  • Terpenes* / pharmacology


  • Antibodies, Antinuclear
  • Autoantibodies
  • Immunoglobulin G
  • Terpenes
  • pristane
  • Interferon-gamma