Tesar V, Jelínková E, Masek Z, Jirsa M, Zabka J, Bartůnková J, Stejskalová A, Janatková I
I interní klinika I. LF UK a VFN, Praha.
Cas Lek Cesk. 1997 Oct 22;136(20):627-32.
Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active ANCA-positive renal vasculitis (ANCA-A). Plasma exchange (PE) may influence the activity of vasculitis not only by removal of pathogenic autoantibodies, but also by lowering of serum levels of circulating cytokines.
Serum levels of IL-1, IL. 1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 pts with active ANCA-positive renal vasculitis (5 pts with Wegener's granulomatosis-WG, 5 pts with microscopic polyangiitis-MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained in the beginning and at the end of the 1st, 3rd and 5th PE and in the samples of filtrate obtained during the same PE. Pts with ANCA had before the 1st PE in comparison with controls higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1. There were increased serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 in pts with MPA and increased serum levels of all measured cytokines and adhesion molecules in pts with WG. At the end of the course of PE there was the decrease of serum levels of IL-ira and VCAM-1 in pts with ANCA and IL-1ra and ICAM-1 in WG. Single PE led in pts with ANCA only to the decrease of serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change of serum levels of IL-1 and IL-8 serum levels of IL-1ra and IL-6 even increased at the end of single PE, in spite of high levels of all cytokines and adhesion molecules in plasmafiltrate.
Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by the course of PE. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with synthetic membrane. Insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.
促炎细胞因子血清水平升高可能导致活动性抗中性粒细胞胞浆抗体相关性肾血管炎（ANCA-A）中的器官损伤。血浆置换（PE）可能不仅通过清除致病性自身抗体，还通过降低循环细胞因子的血清水平来影响血管炎的活动。
在10例活动性抗中性粒细胞胞浆抗体阳性肾血管炎患者（5例韦格纳肉芽肿病-WG，5例显微镜下多血管炎-MPA）接受治疗性血浆置换过程中，采用酶联免疫吸附测定法（ELISA）检测血清白细胞介素-1（IL-1）、白细胞介素-1受体拮抗剂（IL-1ra）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）水平。在第1次、第3次和第5次血浆置换开始时、结束时采集的血清样本以及同一血浆置换过程中采集的滤液样本中检测细胞因子和黏附分子。与对照组相比，抗中性粒细胞胞浆抗体阳性患者在第1次血浆置换前血清IL-1ra、IL-8、ICAM-1和VCAM-1水平较高。显微镜下多血管炎患者血清IL-6、IL-8、ICAM-1和VCAM-1水平升高，韦格纳肉芽肿病患者所有检测的细胞因子和黏附分子血清水平均升高。在血浆置换疗程结束时，抗中性粒细胞胞浆抗体阳性患者血清IL-1ra和VCAM-1水平降低，韦格纳肉芽肿病患者血清IL-1ra和ICAM-1水平降低。单次血浆置换仅使抗中性粒细胞胞浆抗体阳性患者血清ICAM-1和VCAM-1水平降低。另一方面，尽管血浆滤液中所有细胞因子和黏附分子水平较高，但单次血浆置换结束时血清IL-1和IL-8水平无变化，血清IL-1ra和IL-6水平甚至升高。
血浆置换后可溶性黏附分子血清水平降低，但即使经过血浆置换疗程，促炎细胞因子血清水平也未降低。血浆置换对这些物质的清除明显受到其产生增加的抵消，可能是血液与合成膜接触进一步刺激所致。血浆置换对促炎细胞因子清除的影响不足可能部分解释了其在一些抗中性粒细胞胞浆抗体阳性肾血管炎患者中效果有限的原因。
