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首次透析及长期透析对尿毒症相关循环单核细胞白细胞介素-1基础分泌增加及肿瘤坏死因子α的影响

Influence of first and long-term dialysis on uraemia-associated increased basal production of interleukin-1 and tumour necrosis factor alpha by circulating monocytes.

作者信息

Herbelin A, Ureña P, Nguyen A T, Zingraff J, Descamps-Latscha B

机构信息

INSERM U 25, Hôpital Necker, Paris, France.

出版信息

Nephrol Dial Transplant. 1991;6(5):349-57. doi: 10.1093/ndt/6.5.349.

Abstract

In a previous study we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term haemodialysis patients and of tumour necrosis factor alpha (TNF alpha) in both long-term haemodialysis and not-yet-dialysed uraemic patients. The present report investigates the spontaneous capacity of monocytes to produce and secrete these two cytokines in 35 long-term haemodialysis patients and 36 uraemic patients undergoing their first dialysis session. Predialytic cell-associated IL-1 concentrations in freshly isolated monocytes were significantly increased both in long-term haemodialysis and first-dialysis uraemic patients compared to normal individuals. In both groups in comparison to normal individuals, although intracellular TNF alpha could not be detected in freshly isolated monocytes, both extracellular IL-1 and TNF alpha concentrations were greatly increased after 20 h of in vitro culture of monocytes in the absence of exogenous stimulation and in serum-free conditions. However, long-term haemodialysis patients showed higher values of secreted IL-1 than not-yet dialysed uraemic patients. During a single dialysis session a significant increase in both cell-associated and secreted IL-1 but not TNF alpha was observed in long-term haemodialysis patients. In contrast, no change in the concentration of either cytokine could be detected at the end of the first dialysis session in uraemic patients. Our findings strongly suggest that factors related to uraemia could be a sufficient signal to initiate intracellular IL-1 protein synthesis and TNF alpha release by monocytes, but that greater IL-1 release could be stimulated during the periodic haemodialysis procedure.

摘要

在先前的一项研究中,我们证明了长期血液透析患者体内存在循环白细胞介素-1(IL-1),以及在长期血液透析患者和尚未进行透析的尿毒症患者体内均存在肿瘤坏死因子α(TNFα)。本报告调查了35例长期血液透析患者和36例首次接受透析治疗的尿毒症患者中单核细胞产生和分泌这两种细胞因子的自发能力。与正常个体相比,长期血液透析患者和首次透析的尿毒症患者新鲜分离的单核细胞中透析前细胞相关IL-1浓度均显著升高。与正常个体相比,在两组中,尽管在新鲜分离的单核细胞中未检测到细胞内TNFα,但在无外源刺激和无血清条件下对单核细胞进行20小时体外培养后,细胞外IL-1和TNFα浓度均大幅升高。然而,长期血液透析患者分泌的IL-1值高于尚未透析的尿毒症患者。在单次透析过程中,长期血液透析患者的细胞相关和分泌的IL-1均显著增加,但TNFα未增加。相比之下,尿毒症患者在首次透析结束时两种细胞因子的浓度均未检测到变化。我们的研究结果强烈表明,与尿毒症相关的因素可能是启动单核细胞内IL-1蛋白合成和TNFα释放的充分信号,但在定期血液透析过程中可能会刺激更多的IL-1释放。

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