A team of researchers from Argentina and the U.S. have explained how flare-ups in multiple sclerosis patients are intimately related to their melatonin levels, a natural occurring hormone that regulates our sleep/wake cycles – circadian rhythms. The team showed that melatonin alleviates disease symptoms by resetting the immune system, with these finding holding important implications for other autoimmune diseases such as lupus and rheumatoid arthritis. The study, entitled “Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses”, was published in the Cell journal.
Autoimmune diseases result from the unregulated activity of the immune system that misleadingly attacks the body’s own tissues. Most types of these diseases are characterized by periods of disease outbursts and remission, often associated to environmental seasons. In the case of multiple sclerosis patients, relapses are less frequent in the fall and winter, while the opposite is true in the spring and summer. Looking for environmental factors that could contribute for these observations, the authors focused in melatonin. This hormone, besides regulating the circadian cycle also modulates immune responses and its levels have a seasonal dependence – melatonin is produced in higher amounts in the fall and winter when it is darker.
Researchers found that in 132 multiple sclerosis patients, high melatonin levels were associated to alleviation of clinical symptoms. Moreover, in a multiple sclerosis animal model, authors showed that daily injections of melatonin improved clinical symptoms by restoring a healthy balance of T-cells – immune cells type affected in this disease – in mice brains, spinal cords and immune organs. This treatment reduced the levels of harmful T-cells Th17, simultaneously promoting an increase of regulatory T-cells, which keep Th17 activity controlled. Mauricio Farez of the Raúl Carrea Institute for Neurological Research (FLENI) in Argentina, and the first author of the study stated in a news release “The main strength of the study is that we demonstrate with great detail the mechanisms used by melatonin to modulate the immune system. In addition to this, we show the effects of melatonin in an animal model of multiple sclerosis, human cells and patients, connecting basic research with clinical work.“
Melatonin affects T cells transformation by activating signaling pathways involved in inflammatory bowel disease and autoimmune colitis, suggesting that other autoimmune disorders might share the same mechanism. Furthermore, seasonal flare-ups also occur in patients with lupus and rheumatoid arthritis, hinting at broader possible implications of the study. Farez stated “Several melatonin-derived drugs have been used or tested in humans for other conditions such as insomnia. These drugs could potentially be repurposed to modulate inflammation in multiple sclerosis and other inflammatory conditions.” Currently, the researchers are working on a pilot clinical trial targeting melatonin signaling in patients with multiple sclerosis, investigating if there is a relation between melatonin levels and disease development.