Dokoohaki Shima, Ghareghani Majid, Ghanbari Amir, Farhadi Naser, Zibara Kazem, Sadeghi Heibatollah
Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
ER045, Laboratory of Stem Cells, DSST, Biology Department, Faculty of Sciences, Lebanese University, Beirut, Lebanon.
Steroids. 2017 Dec;128:32-36. doi: 10.1016/j.steroids.2017.10.006. Epub 2017 Oct 20.
Corticosteroid therapy is employed in multiple sclerosis (MS), a neurological abnormality characterized by an inflammatory process. Melatonin, a potent sleep-promoting and circadian phase regulatory hormone, is produced mainly in the pineal gland whose inhibition leads to sleep disturbances.
In this study, methylprednisolone (MP) corticosteroid treatment was used in an acute experimental autoimmune encephalomyelitis (EAE) rat model (intraperitoneal, 30 mg/kg) and in MS patients (intravenous, 1000 mg/day), followed by assessing melatonin serum levels.
Results showed that mean clinical scores were significantly improved in MP- versus PBS-treated EAE rats (1.5 vs 4.1, respectively). In addition, MP was found to induce a significant decrease in serum IFN-γ, whereas IL-4 levels were significantly increased, in comparison to PBS-treated EAE rats. The ratio of IFN-γ/IL-4, which acts as an indicator of Th-1/Th-2, was significantly lower in MP treated, compared to PBS treated EAE rats or controls. Moreover, serum levels of melatonin showed a significant decrease in the MP group, compared to normal rats. Moreover, MP therapy for 1 or 2 days resulted in a significant reduction of melatonin serum levels in MS patients.
Since corticosteroids cause a reduction in melatonin serum levels, an important hormone in sleep regulation, their prescription to MS patients should be carefully considered. Corticosteroids could be a cause of insomnia and sleep disturbance in patients receiving this type of medication.
皮质类固醇疗法用于治疗多发性硬化症（MS），这是一种以炎症过程为特征的神经异常疾病。褪黑素是一种强效的促进睡眠和调节昼夜节律的激素，主要由松果体产生，对其抑制会导致睡眠障碍。
在本研究中，甲基强的松龙（MP）皮质类固醇治疗用于急性实验性自身免疫性脑脊髓炎（EAE）大鼠模型（腹腔注射，30mg/kg）和MS患者（静脉注射，1000mg/天），随后评估血清褪黑素水平。
结果显示，与用磷酸盐缓冲盐水（PBS）治疗的EAE大鼠相比，MP治疗的EAE大鼠平均临床评分显著改善（分别为1.5和4.1）。此外，与PBS治疗的EAE大鼠相比，发现MP可导致血清干扰素-γ（IFN-γ）显著降低，而白细胞介素-4（IL-4）水平显著升高。作为辅助性T细胞1/辅助性T细胞2（Th-1/Th-2）指标的IFN-γ/IL-4比值，在MP治疗组中显著低于PBS治疗的EAE大鼠或对照组。此外，与正常大鼠相比，MP组血清褪黑素水平显著降低。此外，MS患者接受1或2天的MP治疗后，血清褪黑素水平显著降低。
由于皮质类固醇会导致血清褪黑素水平降低，而褪黑素是睡眠调节中的一种重要激素，因此在给MS患者开此类药物时应谨慎考虑。皮质类固醇可能是接受此类药物治疗的患者失眠和睡眠障碍的一个原因。
