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

Eur J Immunol. 1999 Jan;29(1):1-10. doi: 10.1002/(SICI)1521-4141(199901)29:01<1::AID-IMMU1>3.0.CO;2-R.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Glomerulonephritis / etiology*
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / physiology*
  • Interleukin-12 / toxicity
  • Interleukin-4 / deficiency
  • Interleukin-4 / genetics
  • Interleukin-4 / physiology
  • Kidney / drug effects
  • Kidney / injuries
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutralization Tests
  • Th1 Cells / immunology*


  • Antibodies, Monoclonal
  • Interleukin-12
  • Interleukin-4