den Broeder Alfons A, Wanten Geert J A, Oyen Wim J G, Naber Ton, van Riel Piet L C M, Barrera Pilar
Department of Rheumatology, University Medical Center Nijmegen, Nijmegen, The Netherlands.
J Rheumatol. 2003 Feb;30(2):232-7.
To evaluate the effects of therapy with a fully human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody on the production of superoxide and other reactive oxygen species (ROS) and on the migration capacity of neutrophils in patients with rheumatoid arthritis (RA).
A total of 29 patients with active RA and 25 healthy controls participated. Assessments were performed at baseline and 2 weeks after the first administration of anti-TNF-alpha. The production of ROS was studied in unstimulated conditions and after stimulation of receptor dependent (serum treated zymosan, STZ) and receptor independent (phorbol mystrate acetate, PMA) pathways by luminol enhanced chemiluminescence. As well, the PMA induced burst production of superoxide was measured using the cytochrome-c reduction assay. Potential changes in neutrophil migration to joints were assessed by scintigraphy with autologous leukocytes.
Baseline production of ROS (both spontaneously and after STZ stimulation) and superoxide and the ex vivo chemotaxis were similar in RA patients (n = 25) and controls (n = 25) and remained unchanged after administration of anti-TNF-alpha. The production of ROS after PMA stimulation was slightly higher in patients than in controls (p = 0.04) and this difference disappeared 2 weeks after the first dose of anti-TNF-alpha (p < 0.05). The scintigraphic study showed that a single dose of anti-TNF-alpha, but not placebo, markedly decreased the influx of leukocytes to inflamed joints.
In patients with RA, anti-TNF-alpha therapy rapidly decreases the influx of leukocytes into inflamed joints but does not impair neutrophil chemotaxis and production of ROS.
评估全人源抗肿瘤坏死因子（TNF）-α单克隆抗体治疗对类风湿关节炎（RA）患者超氧化物及其他活性氧（ROS）生成以及中性粒细胞迁移能力的影响。
共纳入29例活动期RA患者和25例健康对照者。在基线期及首次给予抗TNF-α治疗2周后进行评估。通过鲁米诺增强化学发光法，在未刺激条件下以及刺激受体依赖性（血清处理的酵母聚糖，STZ）和受体非依赖性（佛波酯，PMA）途径后，研究ROS的生成。此外，使用细胞色素c还原试验测量PMA诱导的超氧化物爆发产生。通过自体白细胞闪烁扫描评估中性粒细胞向关节迁移的潜在变化。
RA患者（n = 25）和对照者（n = 25）的ROS（自发及STZ刺激后）、超氧化物基线生成以及体外趋化性相似，给予抗TNF-α后保持不变。PMA刺激后患者的ROS生成略高于对照者（p = 0.04），且在首次给予抗TNF-α剂量2周后这种差异消失（p < 0.05）。闪烁扫描研究显示，单剂量抗TNF-α而非安慰剂可显著减少白细胞向炎症关节的流入。
在RA患者中，抗TNF-α治疗可迅速减少白细胞向炎症关节的流入，但不损害中性粒细胞趋化性及ROS生成。
