Circadian rhythm influences immune responses across a range of diseases

By Sally Robertson, B.Sc.May 20 2019

Researchers in Switzerland have conducted a review of studies looking at how circadian rhythm affects the severity of illnesses ranging from heart attack to allergy.

The review, which mainly included studies of mice, assessed the association between circadian rhythm and immune responses.

As reported in the journal Trends in Immunology, the studies showed that adaptive immune responses – where  specialized immune cells develop to fight pathogens – are controlled by the circadian clock.

Senior author Christoph Scheiermann says this is a striking finding that has potential implications for clinical applications ranging from transplantation through to vaccination.

The review found that the body responds to cues such as light and hormones in ways that influence metabolic and sleep rhythms, as well as other physiological processes. Studies of both animals and humans also found that the white blood cell count fluctuates in a circadian pattern, suggesting that it may be possible in the future to optimize the immune response by manipulating the circadian rhythm.

On looking at studies that compared immune cell circadian rhythms in states of health, inflammation and disease, Scheiermann and colleagues found the following:

Heart attacks

Heart attacks, which are known to occur most commonly in the morning, tend to be more severe when they strike in the morning, compared with when they strike at night.

In studies of mice, the blood monocyte count was found to be higher during the day, compared with at night, when the number of monocytes was higher in infarcted heart tissue. This left the animals with less cardiac protection at night, compared with the protection they had in the morning.

Atherosclerotic plaques

The capacity immune cells have to protect against atherosclerotic plaques can depend on the circadian rhythm of a chemokine protein called CCR2, which is involved in inflammation and immune system function.

In mice, this protein demonstrates  a daily rhythm; it peaks in the morning and depending on the affect it has on immune cells, it can be monitored to track the behavior of white blood cells in cases of atherosclerosis.

Parasitic infections

The ability to fight parasitic infections is dependent on time of day. Mice that had been infected with the worm Trichuris muris were able to fight off the gastrointestinal parasite significantly more quickly if they were infected in the morning rather than in the evening.

Bacterial Toxins

In mice, a bacterial toxin involved in pneumonia triggers an inflammatory response in the lungs, with immune cells recruited in a manner that demonstrates a circadian oscillation pattern.

More monocytes can be drawn into the spleen, liver and peritoneal cavity during the afternoon, meaning the ability to clear bacteria is greatest at this time of day, compared with other times of day.

Allergies

Symptoms of allergy follow a rhythm that is dependent on time of day, with symptoms generally worsening  between midnight and early morning. The molecular clock can therefore drive recruitment of immune cells, asthma outcomes in humans and inflammation of the airways in mice.

Scheiermann says that investigating circadian rhythms in both innate and adaptive immune responses is a valuable way to gain understanding of the physiological interplay and time-dependent succession of events in generating immune responses:

"The challenge lies in how to channel our growing mechanistic understanding of circadian immunology into time-tailored therapies for human patients," he concludes.