Department of Neurology, Multiple Sclerosis Research Division, Keck School of Medicine, University of Southern California, McKibben, Los Angeles, CA 90033, United States.
J Neuroimmunol. 2013 Oct 15;263(1-2):108-15. doi: 10.1016/j.jneuroim.2013.07.008. Epub 2013 Aug 6.
Laquinimod is a novel orally active agent with immunomodulatory properties that was shown to be effective in suppressing disease activity in relapsing-remitting multiple sclerosis patients. Though many mechanisms of action of laquinimod have been described, little is known about the in vivo effects of laquinimod on the functionality of circulating human peripheral blood mononuclear cell populations. We assessed both phenotypical and functional measures of PBMC in a prospective longitudinal analysis comparing laquinimod and placebo treated cohorts. We determined that there were no significant changes in the relative proportion of T-cells, B-cells, monocytes & macrophages, NK-cells, dendritic cells or FoxP3(+) CD25(hi) T-regs in laquinimod treated patients. There were also no significant differences in the proliferative response to PHA or tetanus antigen, or in the inflammatory cytokine bias of these responses. These data demonstrated that there were no significant changes in immune function of PBMC in patients receiving two years of continuous laquinimod therapy who retained a full complement of the major populations of circulating PBMC and retained their capacity to respond to immunologic stimuli.
拉喹莫德是一种新型的具有免疫调节特性的口服药物，在抑制复发缓解型多发性硬化症患者的疾病活动方面显示出疗效。虽然已经描述了拉喹莫德的许多作用机制，但对于拉喹莫德在体内对循环人外周血单个核细胞群体的功能的影响知之甚少。我们在一项前瞻性纵向分析中比较了拉喹莫德和安慰剂治疗组，评估了 PBMC 的表型和功能指标。我们发现，拉喹莫德治疗患者的 T 细胞、B 细胞、单核细胞和巨噬细胞、NK 细胞、树突状细胞或 FoxP3(+)CD25(hi)Tregs 的相对比例没有显著变化。对 PHA 或破伤风抗原的增殖反应，或这些反应的炎症细胞因子偏向也没有显著差异。这些数据表明，在接受两年连续拉喹莫德治疗的患者中，PBMC 的免疫功能没有显著变化，他们保留了循环 PBMC 的主要群体的完整组成，并保留了对免疫刺激的反应能力。
