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

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.