Researchers in Buenos Aires and Boston report that levels of the internal-clock hormone melatonin were higher in fall and winter, and that these higher levels were linked with lower relapse rates in people living with MS.
The team also found that melatonin reduced symptoms of the MS-like disease EAE in mice, reduced immune-cell production of inflammatory immune messengers and increased an anti-inflammatory messenger.
Taken together, these studies identify melatonin as one of several factors that may play a role in MS immune responses. However, more research is needed because taking melatonin supplements has been associated with side effects and interactions with other medications.
The studies were funded by the National MS Society, International Progressive MS Alliance and other agencies, recently reported in Cell (September 10, 2015, 162, 1338-1352).
Background: MS involves immune-system attacks on the brain and spinal cord. Some studies have found that people with relapsing-remitting MS are more likely to have relapses during spring and summer months than in fall or winter. This finding is at apparent odds with other findings that have linked lower levels of vitamin D, which are controlled largely by exposure to sunlight, to higher relapse rates. By that reasoning, one would expect that during spring and summer months when there are longer hours of daylight, people should have fewer relapses. This suggests that additional factors may be at work behind the seasonal variation of MS disease activity.
Drs. Mauricio Farez, Jorge Correale (Raúl Carrea Institute for Neurological Research, Buenos Aires), Francisco Quintana (Harvard Medical School, Boston), and colleagues set out to explore the possible role of the hormone melatonin in seasonal changes in disease activity. Melatonin is naturally produced by the body during darkness, and it is linked to the body’s internal clock and sleep-wake cycles.
This Study: The collaborators conducted a series of studies funded by the National MS Society, International Progressive MS Alliance and other agencies. They report their findings in the journal Cell (September 10, 2015, 162, 1338-1352).
First the team checked the seasonal rates of relapses in a group of 139 people with relapsing-remitting MS and found a 32% reduction in the number of relapses during the fall and winter, in line with some other published studies. Then the team checked urine levels of melatonin (6-sulfatoxymelatonin), and found that melatonin levels were higher in fall and winter, and that higher levels of melatonin were linked with a lower rate of relapses.
Then the team conducted a series of lab studies, finding that administering melatonin to mice could reduce symptoms of the MS-like disease EAE. The team also explored aspects of immune system activity in the mice and in human immune T cells in lab dishes. They found that melatonin reduced the cells’ production of inflammatory immune messengers (such as IL-17) and increased production of an anti-inflammatory messenger (IL-10). They also revealed the complex pathways triggered by melatonin in T cells.
Taken together, these studies identify melatonin as one of several factors that may play a role in MS immune responses.
Comment: Understanding factors that drive MS disease activity will speed the development for better treatments for all forms of the disease. The researchers caution that additional research is needed to translate these findings to better treatments for people with MS. Over-the-counter melatonin supplements are widely available, however, melatonin is a powerful hormone that can cause side effects, including daytime sleepiness, headaches and dizziness, and can interact with other medications.
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