Melatonin levels go up as MS symptoms go down--and as days grow shorter

By John Murphy, MDLinx
Published January 13, 2016

Key Takeaways

Levels of melatonin, whose production depends on seasonal variations of daylight, negatively correlate with multiple sclerosis (MS) activity in humans, according to research published in Cell. That is, as melatonin levels increase with shorter fall and winter days, the severity of clinical symptoms of MS decline.

Researchers put this discovery to the test in lab experiments in mice, and found that treatment with melatonin ameliorated pathology of multiple sclerosis.

However, this finding doesn’t mean that melatonin will prove to be a drug of choice for MS, the investigators cautioned.

“We know that for multiple sclerosis and most autoimmune diseases, both genetic and environmental factors play an important role, but in the last decade or so, most research has focused only on the genetic side of the equation,” said co-senior author Francisco Quintana, PhD, associate professor in the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH), in Boston, MA. “But we wanted to see what environmental factors would reveal to us about this disease. We knew that MS disease activity changed with the seasons. What we’ve uncovered offers an explanation for why that is the case.”

Dr. Quintana and his colleagues, along with investigators at the Center for Research on Neuroimmunological Diseases (CIEN) at the Raul Carrea Institute for Neurological Research (FLENI) in Argentina, began by studying a group of 139 relapsing remitting MS patients. The research team found that during fall and winter, patients experienced a significant improvement in MS symptoms—an observation that’s been found in previous studies.

The team then explored a variety of proposed environmental factors—such as vitamin D levels, UV incidence, and upper respiratory tract infections—possibly linked to MS symptoms. Yet melatonin—whose levels are known to increase with the longer days of the spring and summer, and decrease during the shorter days of the fall and winter—was the factor that was consistently associated with severity of MS symptoms.

The researchers then tested this finding in the lab on both mouse and human cells known to play a role in the immune response that leads to MS symptoms. Melatonin affected the roles of 2 kinds of cells that are important in MS disease progression: pathogenic T cells and regulatory T cells.

“We found that melatonin has a protective effect,” Dr. Quintana said. “It dampens the immune response and helps keep the … pathogenic T cells at bay.” Specifically, melatonin suppresses Th17 cell differentiation and boosts Tr1 generation. It controls the balance between pathogenic T cells and regulatory T cells, they wrote.

Although these results seem to indicate that melatonin could be used as therapy for MS as well as inflammatory bowel disease and other immune-mediated disorders, the pathways involved are complex and likely cross-regulated. So, MS patients should not simply start popping melatonin pills, the authors warned.

“In the future, melatonin or its derivatives may be used in MS patients after appropriate clinical trials are conducted and dosage is established,” Dr. Quintana said. “However, extreme caution should be exercised: our data do not show that melatonin or its analogs are effective in treating MS.”

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