Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
J Neuroimmunol. 2010 Sep 14;226(1-2):104-9. doi: 10.1016/j.jneuroim.2010.05.039. Epub 2010 Jun 9.
Combination therapies with existing or novel drugs for multiple sclerosis (MS) have great clinical potential to improve MS treatment outcomes. Our previous studies had confirmed that the combined treatment of minocycline and prednisone produced beneficial effects partially through preventing the reduction of brain-derived neurotrophic factor and nerve growth factor mRNA expression in the cerebral cortex of experimental autoimmune encephalomyelitis (EAE) mice. As high-dose methylprednisolone administered intravenously has more superior efficacy than oral prednisone and had been provided as a stable therapy for MS patients at the onset of an acute relapse, we further evaluated the effects of combined methylprednisolone and minocycline at suboptimal doses on EAE mice at the acute stage in this study. Interferon gamma (IFN-γ) and interleukin-4 (IL-4), the hallmark cytokines that direct Th1 and Th2 development and play an important role in the pathogenesis of MS as well as EAE, were also assayed. Obtained results showed that combined treatment could successfully attenuate severe clinical deficit and suppress histopathological events in EAE. In addition, reduced IFN-γ and increased IL-4 production/expression were found in the splenocytes culture supernatants and brains of EAE mice by the combined treatment. Our data indicate that the combination of methylprednisolone and minocycline may be a promising therapy for MS.
联合应用现有或新型药物治疗多发性硬化症（MS）具有很大的临床潜力，可以改善 MS 的治疗效果。我们之前的研究已经证实，米诺环素和泼尼松联合治疗通过部分预防实验性自身免疫性脑脊髓炎（EAE）小鼠大脑皮质中脑源性神经营养因子和神经生长因子 mRNA 表达的减少，产生有益的效果。由于高剂量甲基强的松龙静脉内给药比口服泼尼松具有更优越的疗效，并且已作为 MS 患者急性复发时的稳定治疗方法，因此我们在本研究中进一步评估了亚最佳剂量的甲基强的松龙和米诺环素联合治疗对急性 EAE 小鼠的影响。干扰素γ（IFN-γ）和白细胞介素 4（IL-4）是标志性细胞因子，它们指导 Th1 和 Th2 的发展，并在 MS 和 EAE 的发病机制中发挥重要作用，也进行了检测。结果表明，联合治疗可成功减轻 EAE 的严重临床缺陷并抑制其组织病理学事件。此外，通过联合治疗，在 EAE 小鼠的脾细胞培养上清液和脑组织中发现 IFN-γ 减少和 IL-4 产生/表达增加。我们的数据表明，甲基强的松龙和米诺环素的联合治疗可能是 MS 的一种有前途的治疗方法。
