IL-12-dependent, IFN-gamma-independent experimental glomerulonephritis

There is evidence that crescentic glomerulonephritis initiated in rodents b y heterologous antibodies against the glomerular basement membrane (anti-GB M 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 or der to test the role of the two cytokines in anti-GEM glomerulonephritis we used mice lacking either the p40 chain of IL-12 (IL-12-/-) or the IFN-gamm a receptor (IFN-gammaR-/-). Glomerulonephritis was induced by injecting a r abbit anti-GEM serum in mice preimmunized against rabbit IgG. Glomeruloneph ritis was assessed on the basis of proteinuria, immunofluorescence findings and histology. IL-12-/- mice were completely protected against glomerulone phritis. In contrast, IFN-gammaR-/- mice were more severely affected than w ild-type mice. Similarly, cutaneous delayed-type hypersensitivity, a typica l Th1 response, was abolished in the IL-12-/-, mice but increased in the IF N-gammaR-/- mice. The data obtained in IL-12-/- mice support the view that crescentic glomerulonephritis in this model represents a Th1 response. Sinc e IFN-gamma is not required, other products of Th1 cells are likely to medi ate glomerulonephritis. Copyright (C) 2001 S. Karger AG, Basel.