Lin Y F, Chang D M, Shaio M F, Lu K C, Chyr S H, Li B L, Sheih S D
Division of Nephrology, Tri-Service General Hospital, Taipei, Taiwan.
Am J Nephrol. 1996;16(4):293-9. doi: 10.1159/000169012.
Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are closely associated with acute and chronic inflammatory processes in hemodialytic patients. However, the mechanisms concerning cytokine production by monocytes during hemodialysis are still conflicting. With the use of the more specific monoclonal antibody ELISA method, contamination detection and crossover protocol of complement-activating and noncomplement-activating hollow fibers, we were able to confirm augmented II-1 beta production by zymosan-stimulated monocytes with complement-activating hollow fiber as compared to noncomplement-activating hollow fiber before (1,411.9 +/- 865.7 +/- 149.9 pg/ ml/2 x 10(6) monocytes, p < 0.01). at the 15th minute (530.6 +/- 89.1 vs. 247.3 +/- 45.2 pg/ml/2 x 10(6) monocytes, p < 0.01) and at the end of dialysis (1,201.8 +/- 135.1 vs. 707.4 +/- 109.3 pg/ml/2 x 10(6) monocytes, p < 0.01). Similar results were observed with TNF-alpha production. IL-1 beta as well as TNF-alpha production decreased significantly at the 15th min of dialysis, thereafter they increased and approached the baseline levels towards the end of hemodialysis with both hollow fibers. Plasma C3a at the 15th minute correlated positively with postdialysis IL-1 beta and TNF-alpha production, while plasma C3a did not change in patients dialyzed with noncomplement-activating hollow fiber. Complement activation with complement-activating hollow fiber as well as monocyte-membrane interaction with complement-activating and noncomplement-activating hollow fiber might be involved in the pathogenesis of cytokine production during hemodialysis. Uremic toxin removal as well as stimulation of cytokine production inhibitor might contribute to the decreased cytokine production at the 15th minute of hemodialysis and monocyte-membrane interaction with or without complement activation resulted in augmented cytokine production toward the end of hemodialysis with both hollow fibers. We thus concluded that hollow fiber of bioincompatibility triggered much more cytokine production throughout the dialysis procedure.
白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）与血液透析患者的急慢性炎症过程密切相关。然而，关于血液透析过程中单核细胞产生细胞因子的机制仍存在争议。通过使用更特异的单克隆抗体ELISA方法、补体激活和非补体激活中空纤维的污染检测及交叉方案，我们得以证实，与非补体激活中空纤维相比，经酵母聚糖刺激的单核细胞在使用补体激活中空纤维时，IL-1β的产生增加（透析前：1,411.9±865.7±149.9 pg/ml/2×10⁶单核细胞，p<0.01），在第15分钟时（530.6±89.1对247.3±45.2 pg/ml/2×10⁶单核细胞，p<0.01）以及透析结束时（1,201.8±135.1对707.4±109.3 pg/ml/2×10⁶单核细胞，p<0.01）。TNF-α的产生也观察到类似结果。IL-1β以及TNF-α的产生在透析第15分钟时显著下降，此后它们增加，并在透析结束时接近基线水平，两种中空纤维均如此。第15分钟时的血浆C3a与透析后IL-1β和TNF-α的产生呈正相关，而使用非补体激活中空纤维透析的患者血浆C3a无变化。补体激活中空纤维的补体激活以及补体激活和非补体激活中空纤维与单核细胞膜的相互作用可能参与了血液透析过程中细胞因子产生的发病机制。尿毒症毒素的清除以及细胞因子产生抑制剂的刺激可能导致透析第15分钟时细胞因子产生减少，而单核细胞膜与补体激活或未激活的相互作用导致两种中空纤维在透析结束时细胞因子产生增加。因此，我们得出结论，生物不相容性中空纤维在整个透析过程中引发了更多的细胞因子产生。
