Ambrosius Björn, Pitarokoili Kalliopi, Schrewe Lisa, Pedreiturria Xiomara, Motte Jeremias, Gold Ralf
Department of Neurology, St. Josef Hospital, Ruhr-University, Bochum, Germany.
Current address: Department of Neurology, University Hospital Bern, University of Bern, Bern, Switzerland.
J Neuroinflammation. 2017 Apr 26;14(1):92. doi: 10.1186/s12974-017-0864-z.
Fingolimod, a sphingosine-1-phosphate receptor modulator with well-described immunomodulatory properties involving peripheral immune cell trafficking, was the first oral agent approved for the treatment of relapsing remitting multiple sclerosis. Analogous immunomodulatory treatment options for chronic peripheral autoimmune neuropathies are lacking.
We tested fingolimod in the animal model of experimental autoimmune neuritis in Lewis rat. Six to eight-week-old female rats were immunized with P2 peptide and from this day on treated with fingolimod. Histology of the sciatic nerve was done to analyze T cell and macrophage cell count, intercellular adhesion molecule (ICAM) and amyloid precursor protein (APP) expression, as well as apoptotic Schwann cell counts.
Preventive oral treatment with 0.1 mg/kg up to 3 mg/kg fingolimod once daily dissolved in rapeseed oil completely ameliorated clinical neuritis signs. It reduced circulating peripheral blood T cells and infiltrating T cells and macrophages in the sciatic nerve, whereas at the same time, it preserved blood-nerve barrier impermeability. Most importantly, fingolimod showed beneficial properties on the pathogenic process as indicated by fewer apoptotic Schwann cells and a lower amount of amyloid precursor protein indicative of axonal damage at the peak of disease course.
Taken together, orally administered low-dose fingolimod showed an impressive immunomodulatory effect in the rat model of experimental autoimmune neuritis. Our current observations introduce fingolimod as an attractive treatment option for neuritis patients.
芬戈莫德是一种鞘氨醇-1-磷酸受体调节剂，具有涉及外周免疫细胞迁移的免疫调节特性，是首个被批准用于治疗复发缓解型多发性硬化症的口服药物。目前缺乏针对慢性外周自身免疫性神经病的类似免疫调节治疗方案。
我们在Lewis大鼠实验性自身免疫性神经炎动物模型中测试了芬戈莫德。6至8周龄的雌性大鼠用P2肽免疫，从这天起用芬戈莫德治疗。对坐骨神经进行组织学检查，以分析T细胞和巨噬细胞计数、细胞间黏附分子（ICAM）和淀粉样前体蛋白（APP）表达，以及凋亡雪旺细胞计数。
每天一次口服0.1mg/kg至3mg/kg溶解于菜籽油中的芬戈莫德预防性治疗，可完全改善临床神经炎症状。它减少了循环外周血T细胞以及坐骨神经中浸润的T细胞和巨噬细胞，与此同时，它保持了血神经屏障的完整性。最重要的是，芬戈莫德在致病过程中显示出有益特性，表现为凋亡雪旺细胞减少，且在病程高峰期淀粉样前体蛋白量降低，这表明存在轴突损伤。
综上所述，口服低剂量芬戈莫德在实验性自身免疫性神经炎大鼠模型中显示出令人印象深刻的免疫调节作用。我们目前的观察结果表明，芬戈莫德是神经炎患者一种有吸引力的治疗选择。
