Corticosteroid therapy exacerbates the reduction of melatonin in multiple sclerosis

Steroids. 2017 Dec;128:32-36. doi: 10.1016/j.steroids.2017.10.006. Epub 2017 Oct 20.


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.

Keywords: Corticosteroid; Experimental autoimmune encephalomyelitis; Melatonin; Methylprednisolone; Multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Animals
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / blood
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Humans
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Melatonin / metabolism
  • Methylprednisolone / administration & dosage*
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Rats
  • Th1 Cells / drug effects
  • Th2 Cells / drug effects


  • Adrenal Cortex Hormones
  • Interleukin-4
  • Interferon-gamma
  • Melatonin
  • Methylprednisolone