A recent review summarizes how circadian patterns influence our immune systems and, in turn, respiratory diseases.
The body has a central clock, located in the brain, which generates and regulates the body’s circadian patterns and peripheral clocks. The circadian clock ensures that biological processes take place at the optimal time each day. Peripheral clocks are found in almost all cells in the body and coordinate cellular processes. These peripheral circadian clocks are coordinated by the central clock but may become uncoupled, based on external factors such as temperature and food availability.
The idea of biological rhythms or circadian clocks has been around for a long time, but we lacked understanding of how it affects the many complex systems in our bodies. Recent research has shown that disruption of circadian rhythms can, in fact, increase the risk of cardiovascular disease, and even cancers. Furthermore, it has been shown by many groups that the disruption of the circadian clock can lead to dysregulated immune responses. Our immune system is highly dependent on circadian patterns, and accordingly, the numbers of circulating immune cells, their activity, and their secretions fluctuate at different times of the day.
A better understanding of the effects of circadian patterns on our immune system will allow for optimal timing of therapies to best treat patients. A recent review, published by a group from Australia in Sleep Science and Practice, summarizes how circadian patterns can affect inflammation and consequently, respiratory diseases.
What Do We Know So Far?
Each cell type, including immune cells, has machinery comprised of different complexes and proteins that allow them to function differently based on a cycle. Recent research has shown that many immune-associated genes vary in expression when subjects are sleep deprived, showing that disruption to circadian patterns can affect the immune system. Furthermore, there is evidence of daily rhythms in allergic reactions. Experiments have shown that the dysregulation of the clock in rats can lead to an uncoordinated immune response to different challenges. On the other hand, inflammation can affect circadian rhythms as well, which demonstrates the very close links between the two systems.
The Night-Time Factor
Studies suggest that the immune system is more active during rest and becomes less active upon awakening. In humans, immune responses are strong late into the night and in the early morning, which correlates with the worst symptoms in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Accordingly, therapies that are timed to reduce inflammation at certain parts of the night have been proven to be more effective than untimed treatments. In COPD, cigarette smoke and other environmental factors can dysregulate lung circadian patterns, leading to increased inflammation and worsening of the disease. It is also apparent that asthma is largely affected by circadian rhythms, as airway resistance increases during the night, whether or not patients go to sleep. Multiple studies have looked at markers of inflammation, such as white blood cell counts, during the day or night, and observed that patients with nocturnal asthma had more inflammation at night.
This review highlights the complexities of the interactions between circadian patterns and the immune system. Further research is needed to better understand the reciprocal effects of these two systems. There is an increasing amount of research looking at the best times to administer certain therapies so that they are the most effective at reducing inflammation in the context of these diseases. As circadian rhythms greatly affect our immune system, this research can be wide-reaching and hopefully applicable to various other diseases that involve inflammation to improve patient outcomes.
Written by Branson Chen, BHSc
Reference: Comas, M., Gordon, C.J., Oliver, B.G. et al. Sleep Science Practice (2017) 1: 18. https://doi.org/10.1186/s41606-017-0019-2