Amital Howard, Barak Vivian, Winkler Robert E, Rubinow Alan
Department of Medicine D, Meir Medical Center, Tshernichovsky 59, Kfar-Saba, 44281, Israel.
Ann N Y Acad Sci. 2007 Sep;1110:649-60. doi: 10.1196/annals.1423.068.
This article analyzes the serum cytokine profile of a nonrandomized group of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who are destined to be treated with infliximab following failure after failure of different disease-modifiying antirheumatic drugs (DMARDs). Serial serum samples were collected from 11 patients with refractory RA, three with PsA and one with undifferentiated spondyloarthropathy. All were treated with the antitumor necrosis factor (TNF)alpha agent, infliximab, after failing to sustain a clinical remission with conventional DMARDs. Blood samples were obtained at different phases of their therapy. Serum levels of tumor necrosis factor (TNF)alpha, interferon (IFN)gamma, interleukin (IL)-1beta, IL-6, sIL-2R, IL-10, and IL-1 receptor antagonist (IL-1RA) were determined by commercial ELISA kits. Interestingly, only eight of the 11 patients with RA had elevated TNFalpha serum levels (at least once in their serial measurements). Only one was unresponsive to therapy and despite anti-TNFalpha therapy her serum TNFalpha levels remained extremely high. Two RA patients who responded to infliximab had normal TNFalpha serum levels prior to and following infliximab administration. One RA patient improved after infliximab therapy despite unrelenting high serum levels of TNFalpha, IL-6, and sIL-2R. Patients with active PsA who responded to infliximab therapy had sustained high serum TNFalpha levels. In an unselected population of RA and PsA patients, we noticed diverse patterns of serum cytokine profiles. These results imply that the cytokine profiles of RA and PsA are diverse and their pathogenesis is heterogeneous.
本文分析了一组非随机选择的类风湿关节炎(RA)和银屑病关节炎(PsA)患者的血清细胞因子谱,这些患者在使用不同的改善病情抗风湿药物(DMARDs)治疗失败后,注定要接受英夫利昔单抗治疗。从11例难治性RA患者、3例PsA患者和1例未分化脊柱关节病患者中采集系列血清样本。所有患者在使用传统DMARDs未能维持临床缓解后,均接受抗肿瘤坏死因子(TNF)α药物英夫利昔单抗治疗。在治疗的不同阶段采集血样。采用商用ELISA试剂盒测定血清肿瘤坏死因子(TNF)α、干扰素(IFN)γ、白细胞介素(IL)-1β、IL-6、可溶性白细胞介素-2受体(sIL-2R)、IL-10和IL-1受体拮抗剂(IL-1RA)水平。有趣的是,11例RA患者中只有8例血清TNFα水平升高(在系列测量中至少有一次)。只有1例对治疗无反应,尽管接受了抗TNFα治疗,其血清TNFα水平仍然极高。2例对英夫利昔单抗有反应的RA患者在英夫利昔单抗给药前后血清TNFα水平正常。1例RA患者在英夫利昔单抗治疗后病情改善,尽管血清TNFα、IL-6和sIL-2R水平持续居高不下。对英夫利昔单抗治疗有反应的活动性PsA患者血清TNFα水平持续升高。在未经过选择的RA和PsA患者群体中,我们注意到血清细胞因子谱的多种模式。这些结果表明,RA和PsA的细胞因子谱各不相同,其发病机制具有异质性。