Melatonin and the Immune System: The Sleeper Antioxidant

Melatonin is commonly known for its role in sleep. However, the relationship between melatonin and the immune system is just as important for our health.

The Benefits of Melatonin

Few things in life are as important as a good night’s sleep. Healthy sleep cycles contribute to the proper function of numerous body systems including the nervous, cardiovascular, endocrine, gastrointestinal, and of particular significance as of late, the immune system.¹ However, according to Wayne Giles, M.D., from the Centers’ for Disease Control and Prevention (CDC), more than 33% of American adults get less than seven hours.²

When faced with sleep irregularities, many people look to supplementation for support. Melatonin, often referred to as the body’s “sleep hormone,” plays a pivotal role in circadian rhythm regulation and the sleep-wake cycle. Because of this, it often serves as the first choice for many people who have trouble falling or staying asleep.* Surprisingly, melatonin also functions as a potent free radical scavenger and an immune system modulator, highlighting a possible link between a restful night’s sleep and immune system health.*

Melatonin and the Immune System

It turns out that while we sleep, T-cells of the immune system “learn” defenses against foreign agents in a process called adaptive immunity. Pro-inflammatory molecules such as IL-2, IL-6, and IL-12 drive this type of response, and melatonin stimulates the production of all three.*³ Therefore, restful sleep is critical as rising melatonin levels enhance the immune system’s ability to adapt and create new responses.*

Pro-inflammatory cytokines can also contribute to oxidative stress. Melatonin’s unique chemical structure makes it a potent free radical scavenger, enabling one molecule to effectively neutralize up to four different radical oxygen or nitrogen species.*⁴ In this way, melatonin acts , neutralizing harmful effects caused by the release of free radical ions.*⁵ In fact, melatonin is such an excellent antioxidant that it has been retained in virtually every organism from prehistoric prokaryotes to human beings⁵, proving that it is simply too effective not to keep around.*

Additionally, melatonin helps to maintain balanced activity within the immune system. Melatonin is thought to help stimulate the immune system when activity is low or suppressed as well as bring the immune system under control during acute inflammatory responses.*⁵ It seems, melatonin helps the immune system to maintain healthy levels of activity.

Melatonin Production Outside the CNS

Interestingly, melatonin production also takes place outside of the central nervous system. Key immune structures like the spleen, liver, and bone marrow synthesize melatonin. Even some cells of the immune system such as macrophages, mast cells, and natural killer cells can produce melatonin in a paracrine manner.^6,7

In fact, the location of melatonin production depends on what is currently taking place inside the body. In other words, if there is an acute immune response taking place, melatonin production shifts from the brain to the site of the injury where it functions as an antioxidant and anti-inflammatory molecule.*^8,9,10 Indeed, melatonin inhibits production of certain powerful inflammatory markers such as TNF-α, IL-1β, and INF-γ.*^5,9,10 It is no wonder that this incredible molecule continues to emerge as a key player in a healthy immune response as well as a good night’s sleep.

Learn how you can support healthy melatonin levels.

Clinical Contributor

Peter Tracy, Clinical Support Representative

Peter graduated from the University of Central Florida with a double major in Biotechnology and Biomedical Sciences in 2015. He began his career with the Department of Neurosurgery at the Mayo Clinic of Jacksonville, Florida in 2016. Peter joined the Clinical Support Team of Sanesco in November 2020. His interests include functional integrative medicine, exploring the great outdoors, sports, and spending time with his wife, Amina, and their cattle dog, Smokey.

References

1. Banks S, et al. J Clin Sleep Med. 2007;3(5):519-528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978335/
2. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention Online. 2016. www.cdc.gov/media/releases/2016/p0215-enough-sleep.html
3. Srinivasan V, et al. Immunity and Ageing. 2005;2:17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325257/#:~:text=Melatonin%20seems%20to%20play%20a,12%20is%20stimulated%20by%20melatonin.
4. Tan DX, et al. Current Topics in Medicinal Chemistry. 2002;2(2):181-197. https://pubmed.ncbi.nlm.nih.gov/11899100/
5. Carrillo-Vico A, et al. International Journal of Molecular Sciences. 2013;14(4):8638-8683. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645767/
6. Emet M, et al. Eurasian Journal of Medicine. 2016;48(2):135-141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970552/
7. Carrillo-Vico A, et al. FASEB J. 2004;18(3):537-539. https://pubmed.ncbi.nlm.nih.gov/14715696/
8. Markus RP, et al. Neuroimmunomodulation. 2007;14(3-4):126-133. https://pubmed.ncbi.nlm.nih.gov/18073503/
9. Markus RP, et al. International Journal of Molecular Sciences. 2013;14(6):10979-10997. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709713/
10. Markus RP, et al. British Journal of Pharmacology. 2018;175(16):3239-3250. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057910/
11. Pontes GN, et al. Journal of Pineal Research. 2007;43(4):365-371. https://pubmed.ncbi.nlm.nih.gov/17910605/
12. Tarocco, A., et al.Cell Death and Disease 2019;10. 317. https://www.nature.com/articles/s41419-019-1556-7#:~:text=Melatonin%20as%20a%20potent%20and,%2C71%2C72%2C73.
13. Esposito E, et al. Current Neuropharmacology. 2010;8(3):228-242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001216/#R197
14. Tan DX, et al. Molecules. 2015;20(10):18886-18906. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332205/#:~:text=As%20a%20potent%20free%20radical,is%20referred%20as%20its%20cascade.
15. Hardeland, R. Cellular and Molecular Life Sciences.2017;74. 3883–3896. https://link.springer.com/article/10.1007%2Fs00018-017-2615-9#citeas
16. Mayo Foundation for Medical Education and Research. Mayo Clinic Online. 2018. www.mayoclinic.org/diseases-conditions/insomnia/expert-answers/lack-of-sleep/faq-20057757#:~:text=In%20addition%2C%20infection%2Dfighting%20antibodies,blood%20vessel%20(cardiovascular)%20disease