Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil.
Department of Psychobiology, Federal University of São Paulo (UNIFESP-EPM), São Paulo, Brazil.
Int Immunopharmacol. 2019 Oct;75:105809. doi: 10.1016/j.intimp.2019.105809. Epub 2019 Aug 16.
The psychostimulant drug modafinil has been used for many years for the treatment of sleep disorders. Recent studies have indicated that modafinil has immunomodulatory properties in the central nervous system (CNS) and peripheral immune cells. Thus, our aim was to determine the effects of in vivo therapeutic treatment with modafinil on the severity of clinical symptoms and immune response during the acute phase of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis. Modafinil treatment, given after the onset of symptoms, resulted in an improvement of EAE symptoms and motor impairment, which was correlated with reduced cellular infiltrate and a decreased percentage of T helper (Th) 1 cells in the CNS. The spinal cord analysis revealed that modafinil treatment decreased interferon (IFN)-γ and interleukin (IL)-6 protein levels and down regulated genes related to Th1 immunity, such as IFN-γ and TBX21, without affecting Th17-related genes. Our research indicates that therapeutic modafinil treatment has anti-inflammatory properties in an EAE model by inhibiting brain Th1 response, and may be useful as adjuvant treatment for multiple sclerosis.
莫达非尼是一种精神兴奋剂药物,多年来一直被用于治疗睡眠障碍。最近的研究表明,莫达非尼在中枢神经系统(CNS)和外周免疫细胞中具有免疫调节特性。因此,我们的目的是确定在实验性自身免疫性脑脊髓炎(EAE)的急性阶段,即多发性硬化的实验模型中,使用莫达非尼进行体内治疗对临床症状和免疫反应严重程度的影响。在出现症状后开始进行莫达非尼治疗,可改善 EAE 症状和运动障碍,这与细胞浸润减少以及 CNS 中 Th1 细胞的百分比降低相关。脊髓分析表明,莫达非尼治疗降低了干扰素(IFN)-γ和白细胞介素(IL)-6 蛋白水平,并下调了与 Th1 免疫相关的基因,如 IFN-γ 和 TBX21,而不影响与 Th17 相关的基因。我们的研究表明,莫达非尼治疗通过抑制大脑 Th1 反应,在 EAE 模型中具有抗炎特性,可能作为多发性硬化症的辅助治疗方法。