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

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 microliters/min, normal mouse 182 +/- 8 microliters/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 microliters/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 the development of glomerular crescent formation and protects renal function.