Division of Rheumatology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan,
Rheumatol Int. 2014 Mar;34(3):429-33. doi: 10.1007/s00296-013-2778-0. Epub 2013 May 14.
To examine the relationship between serum cytokine levels and response to tocilizumab in patients with RA. The disease status of 21 RA patients was assessed at baseline and after 12 weeks of tocilizumab treatment, using the clinical disease activity index (CDAI). Clinical response to tocilizumab was defined as an improvement of >50% from the baseline CDAI. Serum cytokine levels were quantified using double-ligand ELISA for TNF-α, IL-6, CCL2, CCL3, CXCL8, CXCL10, CX3CL1, and macrophage migration inhibitory factor (MIF). After 12 weeks of tocilizumab treatment, there was a significant overall reduction in RA disease activity (CDAI), from 22.4 ± 11.3 to 9.2 ± 6.6 (p < 0.0001), across the entire patient group. After 12 weeks of tocilizumab treatment, 14 patients achieved a >50% improvement (the responder group), but there were no significant responses in the other 7 patients (the non-responder group). The erythrocyte sedimentation rate levels, the positive % of anti-cyclic citrullinated protein antibody and patients (%) receiving methotrexate in combination with tocilizumab were significantly higher in the responder group than in the non-responder group. Although serum baseline levels of CCL2 and CXCL8 were higher in the responder group than in the non-responder group, there were no significant changes in these chemokine levels after treatment. The serum MIF levels, but not the levels of other cytokines, in the responder group were significantly decreased after tocilizumab treatment. Our results suggest that tocilizumab differentially regulates serum cytokine profiles in patients with RA, and MIF regulation in patients with active RA may be sensitive to anti-IL-6 therapy.
为了研究血清细胞因子水平与 RA 患者对托珠单抗反应之间的关系。在托珠单抗治疗 12 周后，使用临床疾病活动指数（CDAI）评估 21 例 RA 患者的疾病状态。将托珠单抗治疗后 CDAI 较基线改善≥50%定义为临床应答。使用双配体 ELISA 定量检测 TNF-α、IL-6、CCL2、CCL3、CXCL8、CXCL10、CX3CL1 和巨噬细胞移动抑制因子（MIF）的血清细胞因子水平。托珠单抗治疗 12 周后，整个患者组的 RA 疾病活动度（CDAI）均显著降低，从 22.4±11.3 降至 9.2±6.6（p<0.0001）。托珠单抗治疗 12 周后，14 例患者（应答组）达到≥50%的改善，但另外 7 例患者（无应答组）无显著反应。与无应答组相比，应答组的红细胞沉降率水平、抗环瓜氨酸肽抗体阳性率和接受甲氨蝶呤联合托珠单抗治疗的患者比例显著更高。虽然应答组的血清 CCL2 和 CXCL8 基线水平高于无应答组，但治疗后这些趋化因子水平没有显著变化。应答组的血清 MIF 水平，而不是其他细胞因子的水平，在托珠单抗治疗后显著降低。我们的结果表明，托珠单抗在 RA 患者中差异调节血清细胞因子谱，而 MIF 在活动期 RA 患者中的调节可能对抗 IL-6 治疗敏感。
