Ar. Kitching et al., INTERLEUKIN-4 AND INTERLEUKIN-L0 ATTENUATE ESTABLISHED CRESCENTIC GLOMERULONEPHRITIS IN MICE, Kidney international, 52(1), 1997, pp. 52-59
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.