不同透析膜在尿毒症患者白细胞介素-6可溶性受体释放中的作用。

Role of different dialysis membranes in the release of interleukin-6-soluble receptor in uremic patients.

作者信息

Memoli B, Postiglione L, Cianciaruso B, Bisesti V, Cimmaruta C, Marzano L, Minutolo R, Cuomo V, Guida B, Andreucci M, Rossi G

机构信息

Departments of Nephrology, Cellular and Molecular Biology and Pathology, University "Federico II" of Naples, Italy.

出版信息

Kidney Int. 2000 Jul;58(1):417-24. doi: 10.1046/j.1523-1755.2000.00181.x.

DOI:10.1046/j.1523-1755.2000.00181.x

PMID:10886590

Abstract

BACKGROUND

Interleukin-6 (IL-6) exerts its actions through a cell-surface receptor system that consists of two transmembrane subunits: the IL-6 binding glycoprotein gp 80 (IL-6R) and the signal-transducing component (gp 130). Soluble forms of the IL-6R (sIL-6R) are generated by shedding of the membrane-associated proteins. The sIL-6R binds the ligand IL-6 with comparable affinity as the membrane-associated IL-6R and enhances the actions of IL-6.

METHODS

Our aim was to evaluate the role of both uremia and different dialysis membranes on peripheral blood mononuclear cell (PBMC) release (either in absence or in presence of mitogen stimulation) and plasma levels of sIL-6R. Ten patients chronically dialyzed with cuprophan membranes (CU), eight patients on regular dialysis treatment with polymethylmethacrylate (PMMA) membranes, 11 uremic nondialyzed patients (UR), and 12 healthy subjects (CON) were included in the study.

RESULTS

PBMCs harvested from CU spontaneously released significantly (P < 0.01) greater amounts of sIL-6R (881.8 +/- 80.1 pg/mL), as compared with CON (267.5 +/- 26.5 pg/mL), UR (258.4 +/- 38.1 pg/mL), and PMMA (288.4 +/- 24.6 pg/mL). Under mitogenic stimulation, the sIL-6R release was significantly (P < 0.01) increased in all groups. The greater PBMC production of sIL-6R in CU was followed by significantly (P < 0.01) higher levels of circulating soluble receptors (48.7 +/- 2.5 ng/mL, 60%), as compared with CON (30.5 +/- 1.9 ng/mL). UR also showed high circulating levels of sIL-6R (53.3 +/- 5.9 ng/mL), probably secondary to an impaired urinary excretion. Circulating levels of sIL-6R in PMMA were comparable to CON (30.3 +/- 3.3 ng/mL). Either the absence of monocyte activation or the adsorption of sIL-6R on the hydrophobic PMMA surface could explain this finding.

CONCLUSIONS

These results suggest an important role for poor dialysis biocompatibility of CU on the release of sIL-6R, which increases sIL-6R plasma levels, thereby enhancing the inflammatory effects of IL-6.

摘要

背景

白细胞介素 -6（IL -6）通过一种细胞表面受体系统发挥作用，该系统由两个跨膜亚基组成：IL -6结合糖蛋白gp80（IL -6R）和信号转导成分（gp130）。IL -6R的可溶性形式（sIL -6R）是通过膜相关蛋白的脱落产生的。sIL -6R与配体IL -6结合的亲和力与膜相关的IL -6R相当，并增强IL -6的作用。

方法

我们的目的是评估尿毒症和不同透析膜对外周血单个核细胞（PBMC）释放（有无丝裂原刺激）以及sIL -6R血浆水平的作用。本研究纳入了10例用铜仿膜（CU）进行长期透析的患者、8例用聚甲基丙烯酸甲酯（PMMA）膜进行常规透析治疗的患者、11例未透析的尿毒症患者（UR）和12名健康受试者（CON）。

结果

与CON（267.5±26.5 pg/mL）、UR（258.4±38.1 pg/mL）和PMMA（288.4±24.6 pg/mL）相比，从CU采集的PBMC自发释放的sIL -6R量显著更高（P<0.01）（881.8±80.1 pg/mL）。在丝裂原刺激下，所有组的sIL -6R释放均显著增加（P<0.01）。CU中PBMC产生的sIL -6R更多，随后循环可溶性受体水平显著更高（P<0.01）（48.7±2.5 ng/mL，60%），而CON为（30.5±1.9 ng/mL）。UR的sIL -6R循环水平也较高（53.3±5.9 ng/mL），可能继发于尿排泄受损。PMMA中sIL -6R的循环水平与CON相当（30.3±3.3 ng/mL）。单核细胞激活的缺乏或sIL -6R在疏水性PMMA表面的吸附可能解释了这一发现。