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.
Kitching
A R
AR
Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia. richard.kitching@med.monash.edu.au
Tipping
P G
PG
Huang
X R
XR
Mutch
D A
DA
Holdsworth
S R
SR
D000818:Animals; D003404:Creatinine / Q000652:urine; D005337:Fibrin / Q000378:metabolism; D005921:Glomerulonephritis / Q000188:drug therapy*; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000008:administration & dosage / Q000494:pharmacology*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011507:Proteinuria / Q000652:urine; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects
D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D005337:Fibrin; D003404:Creatinine