Interleukin-8 and tumor necrosis factor-alpha are increased in minimal change disease but do not alter albumin permeability

AIMS: Minimal change disease (MCD) is the most common primary nephrotic syndrome in children. Some suggested that interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) are involved in the pathogenesis of MCD. This study was done to see changes of plasma and urinary IL-8, TNF-alpha, and their effects on determination of permeability of glomerular basement membrane (BM) contributed by heparan sulfate proteoglycan (HSPG). METHODS: Study patients consisted of 19 biopsy-proven MCD children aged 2-15 years old. Both plasma, urinary IL-8 and TNF-alpha were measured. Employing the Millicell system, IL-8 and TNF-alpha were screened for the permeability factors. We examined whether IL-8 and TNF-alpha regulated BM HSPG gene expression and HS synthesis in the glomerular epithelial cells (GECs). RESULTS: Urinary IL-8 during relapse was significantly increased when compared with that of during remission or controls (13,996 +/- 2,811 vs. 2,941 +/- 373, 5,331 +/- 640 ng/mg.cr) (p < 0.05). Urinary TNF-alpha during relapse was also significantly increased (364.4 +/- 51.2 vs. 155.3 +/- 20.8, 36.0 +/- 4.5 ng/mg.cr) (p < 0.05). Plasma IL-8 during relapse was significantly increased compared to that during remission(1.19 +/- 0.62 vs. 0.51 +/- 0.42 ng/ml) (p < 0.05). However, the negative results were obtained in the permeability assay using the Millicell system. No difference was seen in BM HSPG gene expression and HS synthesis in the GECs. CONCLUSION: Therefore, it seems that both IL-8 and TNF-alpha may not play a disease-specific role in the pathogenesis of MCD.