肾血管炎和狼疮性肾炎中的细胞因子与黏附分子

Cytokines and adhesion molecules in renal vasculitis and lupus nephritis.

作者信息

Tesar V, Masek Z, Rychlík I, Merta M, Bartůnková J, Stejskalová A, Zabka J, Janatková I, Fuciková T, Dostál C, Becvár R

机构信息

1st Department of Medicine, Charles University, Prague, Czechoslovakia.

出版信息

Nephrol Dial Transplant. 1998 Jul;13(7):1662-7. doi: 10.1093/ndt/13.7.1662.

DOI:10.1093/ndt/13.7.1662

PMID:9681708

Abstract

BACKGROUND

Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules.

METHODS

Plasma levels and urinary excretion of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 14 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated.

RESULTS

Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-alpha (9.27 +/- 3.19% vs 0.58 +/- 0.02%, P < 0.01), IL-6 (120.79 +/- 65.83% vs 1.89 +/- 0.34%, P < 0.01) and increased fractional excretion of IL-8 (23.34 +/- 6.38% vs 2.56 +/- 1.07%, P < 0.01) and sVCAM-1 (0.81 +/- 0.33% vs 0.03 +/- 0.02%, P < 0.01) compared with controls. Urinary excretion of TNF-alpha and IL-6 and fractional excretion of TNFalpha, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-alpha (20.52 +/- 2.01 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05) and sVCAM-1 (1537.88 +/- 276.36 ng/ml vs 692.26 +/- 44.42 ng/ml, P < 0.05) and increased urinary excretion of TNF-alpha (2.81 +/- 0.51 microg/mol creat vs 0.98 +/- 0.05 microg/mol creat, P < 0.01), IL-8 (35.78 +/- 14.03 microg/mol creat vs 12.46 +/- 5.19 microg/mol creat, P < 0.05) and sVCAM-1 (48.98 +/- 20.20 microg/mol creat vs 2.92 +/- 1.35 microg/mol creat, P < 0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-alpha (18.10 +/- 0.57 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05).

CONCLUSIONS

Urinary excretion and fractional excretion, but not plasma levels, of selected pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.

摘要

背景

一些促炎细胞因子和可溶性黏附分子的血浆水平被认为是评估抗中性粒细胞胞浆抗体（ANCA）阳性血管炎和狼疮性肾炎活动度的有用参数。我们推测这些疾病的肾脏活动度通过这些分子的尿排泄和排泄分数能得到更好的反映。

方法

采用酶联免疫吸附测定（ELISA）法测定了14例ANCA阳性肾血管炎患者（8例活动期，ANCA-A；6例缓解期，ANCA-R）、6例活动期狼疮性肾炎（LN）患者、15例IgA肾病（IgAN）患者和9名健康受试者的血浆肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-8以及可溶性细胞黏附分子sICAM-1和sVCAM-1的水平及尿排泄情况。还计算了所选细胞因子和黏附分子的排泄分数。

结果

与对照组相比，ANCA-A患者的TNF-α尿排泄和排泄分数增加（9.27±3.19%对0.58±0.02%，P<0.01）、IL-6（120.79±65.83%对1.89±0.34%，P<0.01），IL-8排泄分数增加（23.34±6.38%对2.56±1.07%，P<0.01）以及sVCAM-1排泄分数增加（0.81±0.33%对0.03±0.02%，P<0.01）。ANCA-A患者的TNF-α和IL-6尿排泄以及TNF-α、IL-6和IL-8排泄分数高于ANCA-R患者。与对照组相比，LN患者的血浆TNF-α（20.52±2.01 pg/ml对12.33±0.23 pg/ml，P<0.05）和sVCAM-1（1537.88±276.36 ng/ml对692.26±44.42 ng/ml，P<0.05）增加，TNF-α（2.81±0.51μg/mol肌酐对0.98±0.05μg/mol肌酐，P<0.01）、IL-8（35.78±14.03μg/mol肌酐对12.46±5.19μg/mol肌酐，P<0.05）和sVCAM-1（48.98±20.20μg/mol肌酐对2.92±1.35μg/mol肌酐，P<0.01）尿排泄增加。与对照组相比，IgAN患者仅血浆TNF-α增加（18.10±0.57 pg/ml对12.33±0.23 pg/ml，P<0.05）。