IL-12-dependent, INF-gamma-independent experimental glomerulonephritis.

There is evidence that crescentic glomerulonephritis initiated in rodents by heterologous antibodies against the glomerular basement membrane (anti-GBM glomerulonephritis) depends on a Th1-type immune reaction. Interleukin 12 (IL-12) is crucial for the development of Th1 helper cells, and interferon gamma (IFN-gamma) is a major proinflammatory product of these cells. In order to test the role of the two cytokines in anti-GBM glomerulonephritis we used mice lacking either the p40 chain of IL-12 (IL-12-/-) or the IFN-gamma receptor (IFN-gammaR-/-). Glomerulonephritis was induced by injecting a rabbit anti-GBM serum in mice preimmunized against rabbit IgG. Glomerulonephritis was assessed on the basis of proteinuria, immunofluorescence findings and histology. IL-12-/- mice were completely protected against glomerulonephritis. In contrast, IFN-gammaR-/- mice were more severely affected than wild-type mice. Similarly, cutaneous delayed-type hypersensitivity, a typical Th1 response, was abolished in the IL-12-/-, mice but increased in the IFN-gammaR-/- mice. The data obtained in IL-12-/- mice support the view that crescentic glomerulonephritis in this model represents a Th1 response. Since IFN-gamma is not required, other products of Th1 cells are likely to mediate glomerulonephritis.
AuthorsM Le Hir, B Ryffel, U Schatzmann
JournalKidney & blood pressure research (Kidney Blood Press Res) Vol. 24 Issue 1 Pg. 27-32 ( 2001) ISSN: 1420-4096 [Print] Switzerland
PMID11174003 (Publication Type: Journal Article)
Chemical References
  • Interleukin-12
  • Interferon-gamma
  • Animals
  • Anti-Glomerular Basement Membrane Disease (etiology, immunology)
  • Gene Deletion
  • Interferon-gamma (genetics, immunology)
  • Interleukin-12 (genetics, immunology)
  • Male
  • Mice
  • Th1 Cells (immunology)
  • Th2 Cells (immunology)

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