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Interleukin-10 inhibits experimental mesangial proliferative glomerulonephritis
A R Kitching1, M Katerelos, S J Mudge
1Centre for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia. richard.kitching@med.monash.edu.au
Clinical and Experimental Immunology
|May 2, 2002
Summary
Interleukin-10 (IL-10) limits experimental mesangial proliferative glomerulonephritis by reducing inflammatory cell recruitment and mesangial cell proliferation. This suggests IL-10 is a potential therapeutic target for this kidney disease.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Conflicting reports exist on interleukin-10 (IL-10) effects on mesangial cells, with both proliferative/antiproliferative and pro/anti-inflammatory actions documented.
- The impact of IL-10 on glomerulonephritis characterized by mesangial proliferation remains unclear.
Purpose of the Study:
- To investigate the potential of IL-10 to limit experimental mesangial proliferative glomerulonephritis.
- To test the hypothesis that IL-10 administration would reduce mesangial cell proliferation in an animal model.
Main Methods:
- Mesangial proliferative glomerulonephritis was induced in rats using anti-Thy 1 antibody.
- IL-10 was administered to experimental rats, and outcomes were compared to control groups.
- Glomerular proliferation was assessed by PCNA and bromodeoxyuridine staining; inflammatory cell influx and gene expression (IL-1beta, ICAM-1, MCP-1, osteopontin) were analyzed.
Main Results:
- IL-10 treatment significantly reduced glomerular cellular proliferation and the number of cells within glomeruli.
- A decrease in glomerular macrophage influx was observed in IL-10 treated rats.
- Renal IL-1beta mRNA and glomerular ICAM-1 expression were reduced, while MCP-1 and osteopontin mRNA levels were unchanged.
Conclusions:
- IL-10 effectively diminishes inflammatory cell recruitment and mesangial cell proliferation in experimental mesangial proliferative glomerulonephritis.
- The anti-proliferative effects of IL-10 on mesangial cells may involve direct actions and macrophage-mediated pathways.
- IL-10 demonstrates potential as a therapeutic agent for glomerulonephritis involving mesangial proliferation.