title: Interferon-gamma 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-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.
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, Gainesville 32610-0221, USA. richahb@medicine.ufl.edu
authors.forename: H B
authors.initials: HB
authors.lastname: Richards
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: J C
authors.initials: JC
authors.lastname: Jennette
authors.forename: B P
authors.initials: BP
authors.lastname: Croker
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: W H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D008181:Lupus Nephritis / Q000139:chemically induced* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout / Q000235:genetics; D013729:Terpenes / Q000494:pharmacology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007074:Immunoglobulin G; D013729:Terpenes; C009042:pristane; D007371:Interferon-gamma