Chronomedicine and Immunity: How Circadian Rhythms Impact Our Bodies’ Immune Systems

Cold and flu season are starting in the southern hemisphere, while allergy season is in full swing in the global north. Both of these are linked to our immune systems, which are built out of many different organs, hormones, and free-roaming, invader-killing cells such as T-cells. Because infection can happen anywhere, our immune systems interact with every tissue in the body. Many of these tissues change considerably over the day, and new lines of research are growing around the ways our body’s sense of time matters in fighting infection, reducing inflammation, responding to autoimmune diseases and allergies, and more.

There are numerous chemical changes that take place throughout the day, driven by our body’s biological clocks — like the ones in the brain and the stomach — and this changing chemistry changes how almost every tissue in the body responds to invaders like viruses (or pollen 🤧) and inflammation. The central clock in our brain, known as the suprachiasmatic nucleus (SCN) in the hypothalamus, sends timekeeping signals throughout the body. Other parts of our bodies also have circadian rhythms, which both take time-of-day cues from the SCN and are also influenced by other activities and signals that give a sense of time to those organs, such as eating for the clock in the stomach.

Recently, researchers discovered circadian rhythms in another part of the hypothalamus, the paraventricular nucleus (PVN). This nucleus is responsible for managing stress and immune responses through fluctuations in hormones called glucocorticoids (GCs).  GCs are so influential on the immune system that they are used in medications for treating illnesses such as allergies, asthma, autoimmune diseases, and sepsis. Release of these and other such hormones were found to suffer disruption from mistimed light and food and general light pollution.

One GC you may have heard of is cortisol, a.k.a. hydrocortisone, when given as a medication. Cortisol has a number of effects on the body. Cortisol prevents the release of substances in the body that cause inflammation, and controlling inflammation plays an important role in recovering from injuries like a fall as well as acute conditions like asthma attacks and fighting infections. Researchers in another study observed a heightened inflammation in humans who were administered lipopolysaccharide (LPS), a strong immune system stimulator, at night versus those receiving LPS during the day.

Beyond hormonal changes, a number of other chemical changes cycle throughout the day, and numerous recent studies discovered time-of-day effects for illness recovery, intensity, and duration. One of the more dramatic examples of such time-of-day effects found a 55% difference in survival rates based on time of infection. In that study, mice were infected with a specific virus at the start of their rest or active period; the population infected at the start of their rest period had a 95% mortality rate, whereas the other group had just 40%. Researchers in multiple human studies found variance in both the levels and behavior of various chemicals important to the immune system among human subjects, adding further items to the list of systems that exhibit clear circadian signals in immune system responses, such as allergies and inflammation.

Our bodies have many natural, daily rhythms that affect the way they respond to injuries, allergens, and infections. While the research on timing-specific disease outcomes among humans is still a young subject, mice recovering from infections demonstrate highly variable outcomes, with one study finding a 55% difference in mortality rate between populations infected at the beginning or end of their daily activity window. Immune response is just one facet of the emerging discipline of chronomedicine, which could be defined as treatment that takes into account the patient’s internal time. In studies, researchers sometimes use very consistent schedules in patients as a proxy for knowing true biological time, but this is, of course, much easier in studies with mice versus humans and also translates poorly to real-world clinical medicine.

At Arcascope, we have developed best-in-class algorithms for determining biological time of day from daily activity and health data and making recommendations to our users that help them achieve their circadian goals. Stay tuned in the coming months for more content related to potential applications of our tech in the world of time-dependent, time-intelligent medicine.


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