INTERLEUKIN-4 AND INTERLEUKIN-L0 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 capac ity of Th2 cytokines, interleukin (IL)-4 and IL-10: to alter the outco me of crescentic GN, after injury is established. Sensitized, control treated mice developed crescentic GN with functional renal injury (117 +/- 20 mu l/min, normal mouse 182 +/- 8 mu l/min, P < 0.05) 10 days a fter an i.v. dose of sheep anti-mouse glomerular basement membrane glo bulin. Combined treatment with IL-4 and IL-10 starting three days afte r initiation of disease significantly reduced glomerular crescent form ation (5.3 +/- 3.2%, control treatment 23.3 +/- 6.4%, P < 0.02) and pr eserved renal function (165 +/- 15 mu l/min, P = 0.57 compared to norm al mice). Treatment with IL-4 alone did not reduce crescent formation or protect renal function. Mice treated with IL-10 showed trends to de creased crescent formation and preservation of renal function. In all cytokine treated groups, the accumulation of effecters of glomerular i njury (CD4+ positive T cells, macrophages and fibrin) was reduced, wit h the combination treatment having the greatest effect. Administration of Th2 cytokines, IL-4 and IL-10 to mice with established GN attenuat es the development of glomerular crescent formation and protects renal function.