Avdeev A S, Novikov A A, Aleksandrova E N, Panasiuk E Iu, Nasonov E L
Klin Med (Mosk). 2014;92(1):28-34.
To evaluate dynamics of cytokine profile characteristics in patients with rheumatoid arthritis (RA) treated with tocilizumab and to identify parameters that can be used to predict the effectiveness of therapy.
42 patients (32 women) aged 43-55 (mean 50.5) years with the duration of disease 23-81 (mean 56.5 months), DAS28 6.4 (5.8-7.05). Each patient was given 6 i/v infusions of 8 mg tocilizumab/day at 4 week intervals in addition to standard therapy. Serum levels of IL-1b, IL-1Pa, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF-basic, G-CSF, GM-CSF, IFN-g, IP-10, MCP-1, MIP-1alpha, MIP-1b, PDGF bb, RANTES, TNF-alpha, VEGF were determined by xMAP multiplex technology.
Good therapeutic effect in accordance with EULAR criteria was documented in 35 and satisfactory one in 7 patients; remission based on CDAI occurred in 33% of the cases. The levels of proinflammatory (IL-1b, -2, -6, -12, -15, -17, IFN-gamma, TNF-alpha) and anti-inflammatory (IL-4, -5, -9, -10, -13) cytokines, hemokines (IL-8, MCP-1, MIP-1a, MIP-1b, MIP-1b) and growth factors (IL-7, GM-CSF, VEGF, FGF basic, IP-10) dropped down by week 24 of the treatment (p < 0.05). Remission based on CDAI was associated with higher baseline levels of IL-1b, -2, GM-CSF and TNF-alpha and good outcome according to EULAR criteria with the rapid fall in IL-10 and -13 levels.
Therapy with tocilizumab results in the rapid and well apparent decrease in the concentration of the practically entire spectrum of cytokines. Measurement of IL-1b, -2, -10, -13, GM-CSF and TNF-alpha may be useful for the prediction of the effectiveness of therapy of RA with tocilizumab.
评估用托珠单抗治疗的类风湿关节炎(RA)患者细胞因子谱特征的动态变化,并确定可用于预测治疗效果的参数。
42例患者(32例女性),年龄43 - 55岁(平均50.5岁),病程23 - 81个月(平均56.5个月),疾病活动评分28(DAS28)为6.4(5.8 - 7.05)。除标准治疗外,每位患者每隔4周静脉注射6次,每次8 mg托珠单抗/天。采用xMAP多重技术测定血清中白细胞介素-1β(IL-1β)、白细胞介素-1受体拮抗剂(IL-1Ra)、白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、白细胞介素-6(IL-6)、白细胞介素-7(IL-7)、白细胞介素-8(IL-8)、白细胞介素-9(IL-9)、白细胞介素-10(IL-10)、白细胞介素-12(IL-12)、白细胞介素-13(IL-13)、白细胞介素-15(IL-15)、白细胞介素-17(IL-17)、嗜酸性粒细胞趋化因子(Eotaxin)、碱性成纤维细胞生长因子(FGF-basic)、粒细胞集落刺激因子(G-CSF)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、干扰素-γ(IFN-γ)、干扰素诱导蛋白10(IP-10)、单核细胞趋化蛋白-1(MCP-1)、巨噬细胞炎性蛋白-1α(MIP-1α)、巨噬细胞炎性蛋白-1β(MIP-1β)、血小板衍生生长因子bb(PDGF bb)、调节激活正常T细胞表达和分泌因子(RANTES)、肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)的水平。
根据欧洲抗风湿病联盟(EULAR)标准,35例患者治疗效果良好,7例患者效果满意;基于临床疾病活动指数(CDAI)的缓解率为33%。治疗至第24周时,促炎细胞因子(IL-1β、IL-2、IL-6、IL-12、IL-15、IL-17、IFN-γ、TNF-α)、抗炎细胞因子(IL-4、IL-5、IL-9、IL-10、IL-13)、趋化因子(IL-8、MCP-1、MIP-1α、MIP-1β、RANTES)和生长因子(IL-7、GM-CSF、VEGF、碱性FGF、IP-10)水平均下降(p < 0.05)。基于CDAI的缓解与基线时较高的IL-1β、IL-2、GM-CSF和TNF-α水平相关,而根据EULAR标准的良好预后与IL-10和IL-13水平的快速下降有关。
托珠单抗治疗可使几乎所有细胞因子的浓度迅速且明显降低。检测IL-1β、IL-2、IL-10、IL-13、GM-CSF和TNF-α可能有助于预测托珠单抗治疗RA的效果。