Interleukin-4 deficiency enhances Th1 responses and crescentic glomerulonephritis in mice

Kidney Int. 1998 Jan;53(1):112-8. doi: 10.1046/j.1523-1755.1998.00733.x.


Evidence suggests that crescentic glomerulonephritis (GN) is due to T helper cell 1 (Th1) directed delayed-type hypersensitivity (DTH)-like injury. As endogenous interleukin (IL)-4, (the pivotal cytokine in Th2 responses) may attenuate Th1 responses in this disease, we compared the development of crescentic GN, induced by a planted antigen, in mice genetically deficient in IL-4 (IL-4-/-) with disease in normal mice (IL-4+/+). IL-4-/- mice developed more severe GN with increased renal impairment (CCr 35 +/- 7 microliters/min vs. 133 +/- 14 microliters/min, P < 0.002) and crescent formation (55.7 +/- 8.4% vs. 4.9 +/- 1.2%, P < 0.002). This was associated with increased glomerular fibrin deposition, glomerular CD4+ T cell infiltration and macrophage recruitment. Systemically, IL-4-/- mice showed an increased antigen specific Th1 response indicated by increased skin DTH, and increased IgG3 and IgG2b. Decreased IgG1 levels indicated a reduced Th2 response. These results demonstrate a protective role for endogenous IL-4 in crescentic GN. They show that IL-4 deficiency promotes crescentic glomerular injury and amplifies local and systemic Th1 responses. They support the hypothesis that crescent formation results from Th1 immune responses to antigens in the glomerulus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glomerulonephritis / etiology
  • Glomerulonephritis / immunology*
  • Hypersensitivity, Delayed
  • Immunoglobulin G / blood
  • Immunoglobulin G / classification
  • Interleukin-4 / deficiency*
  • Kidney Glomerulus / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Sheep
  • Th1 Cells / physiology*


  • Immunoglobulin G
  • Interleukin-4