Zettl U K, Gold R, Toyka K V, Hartung H P
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
J Neuropathol Exp Neurol. 1995 Jul;54(4):540-7. doi: 10.1097/00005072-199507000-00008.
Apoptosis plays a critical role in natural recovery from experimental autoimmune disorders of the nervous system. Here we investigated in experimental autoimmune neuritis (EAN) whether apoptosis is augmented by high-dose corticosteroids, the mainstay of therapeutically active compounds in this group of disorders. Adoptive transfer EAN was induced by intravenous injection of P2-specific T cell blasts. At disease onset or at the maximum of disease two pulses of steroids were given within 12 hours, and animals were sacrificed 6 hours later. Steroid therapy significantly reduced T cell infiltration in sciatic nerve. Treatment on both day 4 and day 7 caused a significant increase of T cell apoptosis (42% vs 8.4% in placebo-treated animals on day 4, p < 0.05; 22.5% vs 7.0% on day 7, p < 0.05) in sciatic nerve as assessed by molecular labeling techniques. In addition, reduction of body weight and thymus weight and augmentation of thymocyte apoptosis were observed in steroid recipients. Steroid treatment markedly reduced cellular proliferation in lymphoid organs as measured by bromodeoxyuridine incorporation. Glucocorticosteroid treatment augments T cell apoptosis in inflammatory lesions of the peripheral nervous system, and this may add to their anti-inflammatory properties mediated by downregulation of cytokine expression.
细胞凋亡在实验性自身免疫性神经系统疾病的自然恢复过程中发挥着关键作用。在此，我们在实验性自身免疫性神经炎（EAN）中研究了高剂量皮质类固醇是否会增强细胞凋亡，皮质类固醇是这类疾病中治疗活性化合物的主要类型。通过静脉注射P2特异性T细胞母细胞诱导过继转移EAN。在疾病发作时或疾病高峰期，在12小时内给予两次类固醇脉冲，6小时后处死动物。类固醇治疗显著减少了坐骨神经中的T细胞浸润。通过分子标记技术评估，在第4天和第7天进行治疗均导致坐骨神经中T细胞凋亡显著增加（第4天，治疗组为42%，安慰剂治疗组为8.4%，p < 0.05；第7天，分别为22.5%和7.0%，p < 0.05）。此外，在接受类固醇治疗的动物中观察到体重和胸腺重量减轻以及胸腺细胞凋亡增加。通过溴脱氧尿苷掺入法测定，类固醇治疗显著降低了淋巴器官中的细胞增殖。糖皮质激素治疗增强了外周神经系统炎症病变中的T细胞凋亡，这可能会增强其通过下调细胞因子表达介导的抗炎特性。
