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Eur J Immunol. 1999 Jan;29(1):1-10.

IL-12 directs severe renal injury, crescent formation and Th1 responses in murine glomerulonephritis.

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1
Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia. richard.kitching@med.monash.edu.au

Abstract

Glomerular crescent formation characterizes severe glomerulonephritis (GN). Evidence suggests that crescent formation results from a delayed-type hypersensitivity-like Th1 response. As IL-12 directs Th1 responses, we tested the hypothesis that IL-12 is important in crescentic GN. Neutralization of IL-12 attenuated crescent formation and cell-mediated injury in C57BL/6 mice sensitized to and challenged with sheep anti-mouse glomerular basement membrane (GBM) globulin. Recombinant IL-12 induced severe crescentic GN with enhanced Th1 responses in C57BL/6 mice in which non-crescentic GN was induced by injecting anti-GBM globulin into naive mice. BALB/c mice do not develop significant crescent formation in these models, due either to regulatory effects of IL-4, or to deficits in IL-12 production/responsiveness. Administering IL-12 to BALB/c mice with GN induced Th1 responses and crescent formation, whereas IL-4-deficient BALB/c mice did not develop cell-mediated crescentic injury when GN was induced in sensitized mice. These results establish a central role for IL-12 in severe crescentic GN.

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