Korean J Nephrol.  2009 Jul;28(4):326-334.

The Role of MCP 1 and IL 6 on the Progress of Crescentic Glomerulonephritis

• Hahn H
• Um EY
• Ha IS

Abstract

PURPOSE
Growing data on the relationship between cytokine expression and the progression of renal diseases make these cytokines potential targets for therapeutic interventions. Weexamined the helper T1-cell- and macrophage-associated cytokines in anti-glomerular basement membrane (GBM) antibody-induced nephritis in mice and their temporal relationships with renal tissue fibrosis.
METHODS
Kidneys were harvested on days 1, 3, 7, 11, and 16 after glomerulonephritis was induced with anti-GBM antibody. The progression of renal fibrosis was serially monitored to quantitate the accumulation of cortical extracellular matrix, and various cytokines were measured simultaneously.
RESULTS
A single injection of anti-GBM antibody successfully produced severe crescentic glomerulonephritis. Proteinuria increased abruptly and both mesangial matrix expansion and interstitial fibrosis progressed rapidly. Cortical fibronectin and type III collagen increased continuously, reaching a peak on day 7, and the deposition of type III collagen followed the same pattern, in parallel with that of urinary transforming growth factor 1 (TGF-1) expression. Serial cytokine measurements revealed a sustained increase in interleukin (IL) 6 and monocyte chemoattractant protein 1 (MCP1) from day 3, but neither IL12, IL18, nor interferon changed significantly. Real-time polymerase chain reaction confirmed these features at the transcription level.
CONCLUSION
MCP1 and IL6 correlated with the progression of renal fibrosis, with no increase in Th1- inducing cytokines. This confirms MCP1 and IL6 as attractive therapeutic targets for renal fibrosis in crescentic glomerulonephritis.

Keyword

Anti-glomerular basement membrane disease; Fibrosis; Interleukin-6; Monocyte chemoattractant protein-1

MeSH Terms

Animals
Anti-Glomerular Basement Membrane Disease
Autoantibodies
Basement Membrane
Chemokine CCL2
Collagen Type III
Cytokines
Extracellular Matrix
Fibronectins
Fibrosis
Glomerulonephritis
Interferons
Interleukin-12
Interleukin-18
Interleukin-6
Interleukins
Kidney
Mice
Nephritis
Proteinuria
Real-Time Polymerase Chain Reaction
Transforming Growth Factors
Autoantibodies
Chemokine CCL2
Collagen Type III
Cytokines
Fibronectins
Interferons
Interleukin-12
Interleukin-18
Interleukin-6
Interleukins
Transforming Growth Factors