Interleukin-4 and interleukin-10 attenuate established crescentic glomerulonephritis in mice

Abstract

Crescentic glomerulonephritis (GN) has immunopathological features of delayed type hypersensitivity (DTH) and results from a T helper cell 1 (Th1) dependent immune response. The current study examined the capacity of Th2 cytokines, interleukin (IL)-4 and IL-10, to alter the outcome of crescentic GN, after injury is established. Sensitized, control treated mice developed crescentic GN with functional renal injury (117 ± 20 μl/min, normal mouse 182 ± 8 μl/min, P < 0.05) 10 days after an i.v. dose of sheep anti-mouse glomerular basement membrane globulin. Combined treatment with IL-4 and IL- 10 starting three days after initiation of disease significantly reduced glomerular crescent formation (5.3 ± 3.2%, control treatment 23.3 ± 6.4%. P < 0.02) and preserved renal function (165 ± 15 μl/min. P = 0.57 compared to normal mice). Treatment with IL-4 alone did not reduce crescent formation or protect renal function. Mice treated with IL-10 showed trends to decreased crescent formation and preservation of renal function. In all cytokine treated groups, the accumulation of effectors of glomerular injury (CD4+ positive T cells, macrophages and fibrin) was reduced, with the combination treatment having the greatest effect. Administration of Th2 cytokines IL-4 and IL-10 to mice with established GN attenuates lilt development of glomerular crescent formation and protects renal function.