Kopadze T, Döbert M, Leussink V I, Dehmel T, Kieseier B C
Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine University, Düsseldorf, Germany.
Eur J Neurol. 2009 Mar;16(3):409-12. doi: 10.1111/j.1468-1331.2008.02433.x.
Damage of the blood-brain barrier and the migration of immunocompetent cells into the CNS represent key events in the immunopathogenesis of multiple sclerosis (MS). Cladribine is an immunosuppressive drug currently investigated in a phase-III clinical trial for relapsing-remitting MS. However, its precise mode of action remains elusive so far.
Peripheral blood mononuclear cells (PBMCs) were isolated from five patients with MS and five healthy donors. PBMCs were treated with cladribine in vitro. The migratory capacity was studied in an in vitro Boyden chamber assay; cells and their rate of migration were analyzed by light microscopy and flow cytometry.
Cladribine decreased the migratory capacity of CD14(+) monocytes, as well as of CD4(+) and CD8(+) T lymphocytes. T lymphocytes were affected more than monocytes. There was no difference in this effect when comparing mononuclear cells from MS patients with cells from healthy controls.
Cladribine might achieve, at least in part, its clinical and paraclinical efficacy by inhibiting the migration of inflammatory cells into and within the CNS.
血脑屏障的破坏以及免疫活性细胞向中枢神经系统的迁移是多发性硬化症（MS）免疫发病机制中的关键事件。克拉屈滨是一种免疫抑制药物，目前正在进行一项针对复发缓解型MS的III期临床试验。然而，其确切的作用方式至今仍不清楚。
从5例MS患者和5名健康供体中分离外周血单个核细胞（PBMC）。PBMC在体外接受克拉屈滨处理。在体外Boyden小室试验中研究其迁移能力；通过光学显微镜和流式细胞术分析细胞及其迁移速率。
克拉屈滨降低了CD14(+)单核细胞以及CD4(+)和CD8(+) T淋巴细胞的迁移能力。T淋巴细胞比单核细胞受影响更大。比较MS患者的单核细胞与健康对照者的细胞时，这种作用没有差异。
克拉屈滨可能至少部分通过抑制炎性细胞向中枢神经系统内及中枢神经系统内的迁移来实现其临床和临床前疗效。
