Interleukin-11 reduces renal injury and glomerular NF-kappa B activity in murine experimental glomerulonephritis.
OBJECTIVE
There is now considerable evidence implicating T cells and macrophages in glomerular injury in crescentic glomerulonephritis. Recently, it has been shown that interleukin-11 (IL-11) has an immune modulatory function through its effect on both macrophages and T cells. We, therefore, examined the therapeutic effect of IL-11 in a murine model of experimental glomerulonephritis.


METHODS
Accelerated nephrotoxic nephritis was induced in C57BL/6 mice. IL-11 at a dose of 0.5 mg/kg/day (n = 10) in vehicle was given daily subcutaneously from the day of sensitization until day 14 after initiation of glomerulonephritis. Control mice (n = 10) received injection of vehicle alone with the same schedule.


RESULTS
IL-11 treatment markedly decreased albuminuria (6.2 +/- 1.9 vs. 18.2 +/- 4.5 mg/day, p < 0.05), the number of glomerular macrophages (1.1 +/- 0.2 vs. 1.7 +/- 0.3 cells/glomerular cross-section, p < 0.05) and glomerular fibrin deposition (fibrin score 0.9 +/- 0.3 vs. 2 +/- 0.3, p < 0.05). There was no difference in the glomerular T cell numbers between the IL-11-treated and the vehicle group. Glomerular NF-kappaB activity was markedly suppressed by 75% in the treated group (p = 0.0015).


CONCLUSIONS
In this study, we provide the first in vivo evidence that IL-11 treatment decreases glomerular NF-kappaB activity and reduces renal injury in experimental glomerulonephritis.
Lai
P C
PC
Kidney Institute, Department of Nephrology, CGMH, Taipei, Taiwan.
Smith
J
J
Bhangal
G
G
Chaudhry
K A
KA
Chaudhry
A N
AN
Keith
J C
JC
Tam
F W K
FW
Pusey
C D
CD
Cook
H T
HT
D000419:Albuminuria / Q000188:drug therapy; D000818:Animals; D002452:Cell Count; D005340:Fibrinogen / Q000032:analysis; D005921:Glomerulonephritis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D007074:Immunoglobulin G / Q000097:blood; D007136:Immunoglobulins / Q000032:analysis; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000494:pharmacology / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D018655:Lymphocyte Count; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes
D007074:Immunoglobulin G; D007136:Immunoglobulins; D017370:Interleukin-11; D016328:NF-kappa B; D011994:Recombinant Proteins; D005340:Fibrinogen