Melatonin improves outcomes in mouse model of MS

Research Summary: Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis

The background

Melatonin is a hormone produced by the pineal gland, a small endocrine gland located in the centre of the brain.  It is well known as a molecule that is involved in disturbances in sleep patterns and has been previously reported to be associated with fatigue in people with multiple sclerosis.  However, more recent information suggests that it may play a larger role in MS.   Studies have shown that melatonin can impact on many aspects of the immune system, including shifting it away from the inflammatory, autoimmune state known to cause problems in MS.  As melatonin levels are also decreased in people with MS, previous studies have examined whether treatment with melatonin can protect mice from developing the animal model of MS (experimental autoimmune encephalomyelitis or EAE).  These trials found that melatonin could indeed inhibit the onset of EAE in mice.  However, very little is known about the potential therapeutic potential of high-dose melatonin for the treatment of MS.

The study

In this study, conducted at the National Defense Medical Center in Taiwan, researchers examined the use of melatonin to treat MS using a mouse model.  Mice were given EAE by injection with a common segment of a myelin peptide known to induce the disease.  The mice were then treated with a high-dose of melatonin after 9, 11 and 13 days.  The level of disability in the mice was measured, as well as the levels of immune cells in the CNS and the cytokines that they expressed.  Cytokines are chemical messengers of the immune system that help to determine the type of response generated, which makes them an important factor to examine when assessing a potential treatment.

The findings

Treatment with melatonin resulted in the following:

• Significant reduction in the clinical severity of EAE in the mice over the 30 days of the experiment, compared to mice that were untreated

• Decreased numbers of immune cells entering the brain and spinal cord of mice treated with melatonin compared to untreated mice.  The overall numbers of lymphocytes did not change between the groups.

• Decreased levels of pro-inflammatory cytokines (interferon-gamma and IL-17), which are known to be important in the disease process in MS.  This was shown in the brain (for both) and in the spinal cord (for IL-17).

• Increased levels of IL-10 in the spleen by regulatory T cells.  It is thought that this improved function of regulatory T cells may be how melatonin influences the immune system.

The outcomes

This study has shown that high-dose melatonin treatment, after the induction of EAE in mice, can result in improved clinical outcomes.  In addition to this, a number of effects on the immune system were observed in the mice treated with melatonin, which could help explain the reduction in disability seen.  As this study is performed in mice, it is unclear yet whether similar effects will be seen in people with MS.  However, it does provide evidence that human trials with melatonin should be considered.

The abstract of the study can be viewed here.