Corticosteroid therapy exacerbates the reduction of melatonin in multiple sclerosis
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Updated: Feb 20, 2026

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Shima Dokoohaki1, Majid Ghareghani1, Amir Ghanbari1
1Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
Objectives:
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.
Methods:
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.
Key Findings:
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.
Conclusions:
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.
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