The Circadian Rhythm and the Immune System

What is circadian rhythm?

The term circadian rhythm was coined to describe the oscillations in body functions observed in humans during 24 hours. The function of the circadian rhythm is to act as a regulator of cells and coordinate the internal physiological and behavioral processes in humans.

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It is argued that the autonomous rhythms must align with the earth’s daily rotation to regulate sleep/wake cycles in humans in line with light changes within the environment. Research suggests that the circadian rhythm is central to human evolution, allowing us to adapt and anticipate environmental changes such as temperature, radiation, and the availability of food.

Dysfunction in circadian rhythms can cause a range of issues such as disturbances in sleep/wake cycles and mood disorders.

The function of the circadian rhythm has been well researched, with contemporary work analyzing the relationship between the immune system and the circadian rhythm.

The circadian rhythm and the immune system

Researchers from Switzerland have recently published a review investigating the link between the circadian rhythm and the development of illnesses such as allergies and cardiovascular difficulties such as heart attacks.

The paper, containing mainly mice studies, found there to be a relationship between the immune system and the circadian rhythm. Specifically, the studies found that adaptive immune responses - whereby specialized immune cells are synthesized to fight invading pathogens – are regulated by the circadian clock.

Based on the research, it is suggested that the body’s response to cues, for example, hormones and light, affects sleep patterns and metabolic processes, amongst other biological activities. The researchers found the circadian rhythm to be implicated in heart attacks, atherosclerotic plaques, infections and toxins, and allergies.

Heart attacks

The researchers found that heart attacks occur more commonly and severely in the morning, in comparison to at night. In animal studies, mice were found to have higher levels of blood monocytes during the daytime. Experiments showed that mice had more monocytes and larger infarctions during the night than during the day.

Atherosclerotic plaques

The immune system produces cells that help to protect against plaques that build up in the arteries. Research has found that the extent to which these cells are effective in upholding this aim is dependent on the circadian rhythms of CCR2 – a chemokine protein. CCR2 is typically involved in the function of the immune system and inflammatory processes.

Mice studies have found the protein to follow a daily rhythm. Specifically, it is suggested to be highest in the morning. Based on its implications on immune cells, it has been found to monitor white blood cells involved in atherosclerosis.

Infections

Mice appear to be differently able to respond to parasite infections depending on the time of day they are exposed. Mice responded to parasite infections with Trichuris muris more quickly when exposed in the morning compared to the evening.

Toxins

Animal studies have found that responses to toxins may be greater in the afternoon. Mice infected with a bacterial toxin that triggers pulmonary inflammation respond differently depending on the time of exposure. If exposed in the afternoon, a larger number of monocytes were drawn into the peritoneal cavity, liver, and spleen resulting in a greater ability to fight the bacteria, compared to other periods of the day.

Allergies

Allergy symptoms tend to be worst between midnight and early morning. Mast cell and eosinophil expression appear to vary based on circadian rhythms in mice.

Sepsis

Researchers have found that the severity of sepsis infections may be worse during the evening compared to the morning. Cell adhesion expression and neutrophil infiltration response to lipopolysaccharide septic shock were found to be higher in the evening. This worsening parallels with an increased risk of mortality during that time.

This relationship between the immune system and circadian rhythm aligns with similar ones found between other bodily systems. For example, within the cardiovascular system, research has reported that in the morning compared to the night time individuals have: a higher heart rate, higher blood pressure, vasoconstriction, and a reduction in parasympathetic tone and thrombolytic activity, .

Sources

Reddy, S., & Sharma, S. (2018). Physiology, Circadian Rhythm. Stat Pearls. https://www.ncbi.nlm.nih.gov/books/NBK519507/

Scheiermann, C., Kunisaki, Y., & Frenette, P. S. (2014). Circadian control of the immune system. Nature Reviews Immunology. DOI: 10.1038/nri3386

Farhud, D., & Aryan, Z. (2018). Circadian Rhythm, Lifestyle and Health: A Narrative Review. Iranian Journal of Public Health. ncbi.nlm.nih.gov/pmc/articles/PMC6123576/

Thosar, S. S., Butler, M. P., & Shea, S. A. (2018). Role of the circadian system in cardiovascular disease.

Pick, R., He, W., Chen, C. S., & Scheiermann, C. (2019). Time-of-Day-Dependent Trafficking and Function of Leukocyte subsets. Trends in Immunology. DOI: https://doi.org/10.1016/j.it.2019.03.010

Further Reading

Last Updated: Nov 27, 2019

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