interleukin-8 and Nephrosis--Lipoid

To study the therapeutic effect of Lespedeza Michx in experimental rat model of minimal change nephropathy (MCN).. The rat MCN model was reproduced by tail-intravenous injection of Adriamycin. The treatment effect of Lespedeza Michx was determined by the detection of urine protein collection for 24 hours, malondialdehyde (MDA), superoxide dismutase (SOD), ATCO, IL-8, TNF-alpha in serum, and renal histopathological changes were observed by microscope.. Lespedeza Michx could decrease the contents of urine proteinuria, MDA, IL-8, and TNF-alpha in serum, increase SOD level and improved the pathological change of glomeruli.. Lespedeza Michx was effective on MCN.

Topics: Animals; Doxorubicin; Flavonoids; Interleukin-8; Kidney Glomerulus; Lespedeza; Male; Malondialdehyde; Nephrosis, Lipoid; Random Allocation; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Proteinuria in idiopathic minimal lesion nephrotic syndrome (IMLNS) is presumed to be due to the effect of circulating factors on glomerular permeability to plasma proteins. This study examines the expression of messenger ribonucleic acid (mRNA) for cytokines thought to mediate glomerular inflammation during different stages of the nephrotic syndrome.. Messenger RNA expression and stability from peripheral blood mononuclear cells of IMLNS patients in relapse and in remission, and age matched normal controls were measured using a ribonuclease protection assay (RPA). The spontaneous and Interleukin 2 (IL-2) stimulated mRNA expression were studied.. Spontaneous mRNA expression for Interleukin 8 (IL-8) from IMLNS patients in relapse was significantly increased when compared to IMLNS patients in remission and normal controls (p < 0.05). After 14 h of IL-2 stimulation, mRNA IL-8 levels expressed by IMLNS PBMC patients in remission were not different from those observed in normal controls. However, after 5 days of PBMC incubation, a significant increase in mRNA for IL-8 in IMLNS patients compared to controls was found (p < 0.01). Stability assay demonstrated that IL-8 mRNA transcript from the nephrotic patients remained higher than those from controls and showed a significantly prolonged life t(1/2) (p = 0.02).. IL-8 mRNA expression is increased in IMLNS patients in relapse. Moreover, stability studies show that IL-8 mRNA life t(1/2) is prolonged due to altered post-transcriptional regulation. This finding may explain the elevated serum IL-8 levels observed in these patients during relapse and may have pathogenic significance since IL-8 has been shown to induce proteinuria in the experimental animal.

Topics: Adolescent; Adult; Child; Child, Preschool; Cloning, Molecular; Cytokines; Down-Regulation; Female; Humans; Interleukin-8; Male; Nephrosis, Lipoid; RNA Processing, Post-Transcriptional; RNA, Messenger

Supernatant factor from peripheral blood mononuclear cell (PBMC) cultures of idiopathic minimal lesion nephrotic syndrome (IMLNS) patients in relapse induces in vivo albuminuria and increases 35sulfate uptake by glomerular basement membrane (GBM) in rats. The purpose of this study was to evaluate the effect of anti-interleukin 8 (IL8) neutralizing antibody on the effects induced by the supernatant factor. Supernatant factor collected from six cultures of PBMC from IMLNS patients in relapse were combined and aliquotted into two samples. Anti-IL8 neutralizing antibody (750 ng) was added to one. Supernatant factor or supernatant factor and anti-IL8 antibody were infused for 5 days into the left renal artery of Wistar rats using an osmotic pump. On the last day of infusion, rats were injected with 35sulfate (1.0 mCi/200 g) intraperitoneally and killed after 8 h. Glomeruli were isolated and GBM obtained. There was a significant increase in 35sulfate uptake of the infused kidney (169 +/- 52 cpm/mg dry glomerular weight, mean +/- SEM) compared with the uptake seen in the contralateral kidney (116 +/- 41, P < 0.05) when the supernatant factor was infused alone. No significant differences in 35sulfate incorporation were seen between infused kidney (173 +/- 5) and contralateral kidney (190 +/- 49) when supernatant factor and anti-IL8 antibody were administered. A significant increase in albuminuria was seen on the last day of infusion (0.43 +/- 0.11 albumin/ creatinine ratio, mean +/- SEM) compared with the ratio prior to infusion of the supernatant factor alone (0.18 +/- 0.03, P <0.05). No significant differences in urinary albumin/creatinine ratios prior to and on the 5th day of infusion were seen when the supernatant factor was administered with anti-IL8 antibody. Supernatant factor effects were abolished by the addition of anti-IL8 neutralizing antibody, suggesting that the described effects are mediated by IL8.

Topics: Adolescent; Adult; Albuminuria; Animals; Antibodies; Child; Child, Preschool; Female; Humans; Infant; Interleukin-8; Kidney Glomerulus; Leukocytes, Mononuclear; Male; Nephrosis, Lipoid; Rats; Sulfates

We studied the interleukin 8 (IL-8) gene expression by peripheral blood mononuclear cells (PBMC) and the IL-8 serum concentration in patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) and other glomerulopathies. PBMC from eight of the nine (IMLNS) patients in relapse demonstrated the presence of IL-8 mRNA. All three IMLNS patients in remission (P = 0.0026 when compared to patients in relapse) and the two patients with nephrotic syndrome with other glomerulopathies failed to elicit an IL-8 mRNA response. Eleven of the 12 IMLNS patients in relapse showed IL-8 serum concentration above the level of detection. Only one of the seven patients in remission had detectable serum levels of IL-8 (P = 0.0033 when compared to levels from IMLNS patients in relapse). IL-8 serum levels were not detectable in three patients with nephrotic syndrome and other glomerulopathies. Supernatants of PBMC cultures from IMLNS patients in relapse increased the 35sulfate uptake by rat GBM. This effect was abolished by the addition of anti-IL-8 neutralizing antibody to the culture media and reproduced by the addition to the media of IL-8 in concentrations found in the serum of IMLNS patients in relapse. Finally, the effect of IL-8 on the 35sulfate turnover of the glomerular basement membrane (GBM) sulfated compounds was evaluated in vitro. A significant decrease in the percentage of residual 35sulfate incorporated in the GBM (41 +/- 5, mean +/- SEM) was observed in cultures treated with IL-8 as compared to those that were not treated with IL-8 (58 +/- 8, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Animals; Basement Membrane; Child; Child, Preschool; Female; Gene Expression; Glomerulonephritis; Humans; Interleukin-8; Kidney Glomerulus; Leukocytes, Mononuclear; Male; Nephrosis, Lipoid; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Recurrence; RNA, Messenger; Sulfates