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Kidney Int. 1998 Jan;53(1):112-8.

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

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

Abstract

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.

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