Sleep well, don’t dwell: The role of sleep and stress in immune health

Recent global health concerns have reminded us of the importance of taking steps to ensure our own immune health promotion. In a fast-paced high-tech world that seems to evolve daily, some of the most important health promoting strategies remain relatively basic, timeless, and are ones your grandmothers’ grandmother would understand. Progress in science has afforded us insight into how these affect our health but the overall strategies themselves remain the same as they have for decades. Two strategies to consider in promoting immune health are sleep and stress management.

Harvard Health(1) outlined suggestions for basic health action steps in cultivating immune health. Most of these suggestions affect not only immune health but positively affect overall general health. These include:

• Don’t smoke.
• Eat a diet high in fruits and vegetables.
• Exercise regularly.
• Maintain a healthy weight.
• If you drink alcohol, drink only in moderation.
• Get adequate sleep.
• Take steps to avoid infection, such as washing your hands frequently, cooking meats thoroughly.
• Try to minimize stress.

The goal of this review is to examine both sleep and stress, two fundamental and basic lifestyle factors, that influence your immune health.

SLEEP
Sleep is interconnected to most all physiological processes in the body, when prioritizing a place to start in your health promotion, restorative sleep should be at the top of the list. In the past, the role sleep played in health may have not received the attention it deserved, in fact in a work focused society, the need for sleep almost signified a weakness. Some even boast about their ability to function on little sleep almost inferring it as a symbol of strength and productivity. It is worth rethinking the value of sleep now that it has been shown that chronically having 5 hours or less of sleep per night increased mortality, and just three consecutive nights of less than 7 hours of sleep resulted in effects similar to missing a full night’s sleep(2).

Sleep and immune function have been described a bidirectional in their effect. Sleep has a direct impact on immune function, whilst immune activation also has an impact on sleep. A microbial immune challenge has shown to increase both the intensity and duration of sleep, while enhanced sleep also improves host defense, and actually lowered infection risk. It is postulated these are intimately related through hormonal regulation, including stress hormones such as cortisol, adrenalin, noradrenaline, and growth hormone. Healthy sleep patterns also promote inflammatory homeostasis. Chronic sleep loss not only drives up inflammation but also promotes immunodeficiency. Reduced sleep resulted in a lowered response to vaccination to influenza virus, it also increased the susceptibility to the common cold. Sleep not only impacts primary responses to infection, it also impacts the formation of antigenic memory(3).

Getting 8 hours of quality sleep influences levels of systemic inflammation and immune system function. Several studies have already confirmed the negative effects increasing levels of inflammation has on immune health.

Irwin and Opp(4) reviewed substantial evidence supporting the homeostatic relationship between sleep disturbances and inflammatory disease risk. Circadian rhythm is linked to quality sleep. Circadian rhythm disruptions magnify inflammatory responses to endotoxic challenge. Chronic jetlag and shift work displayed an upregulation in inflammatory gene expression. Those suffering persistent sleep loss (insomniacs, alcoholics, stress, aging) show a shift to enhanced proinflammatory cytokines not just temporarily but constantly(3).

Sleep has stages we pass through in a sequential order with individual variability in how long we spend in each stage. Slow wave sleep (SWS) known as stage 3-4, is deep restorative sleep. This is the time our bodies are healing, repairing, and conducting surveillance Disturbances such as inflammation or circadian rhythm disruption reduces SWS and increases REM sleep (less deep sleep and more dream sleep) resulting in a decrease in immune response and increasing risk for infections. Proper immune surveillance becomes disrupted with poor sleep. Insomniacs show a decrease in immune T cells (CD3+, CD4+, CD8+) and a reduction in natural killer cell activity (3). These alternations impact the ability of the immune system to respond to a challenge.

The greatest amount of time in SWS occurs in the first part of nocturnal sleep and declines as the night continues. Retiring around 10pm has been shown to increase time spent in SWS restorative sleep. There appears to be a sweet spot as to when you should go to sleep. There is often a window of opportunity to pay attention to. It’s not uncommon to feel a bit sleepy around 9-10pm and then after this time has passed, a second wind of wakefulness hits. It would be better to capitalize on the time you start to feel sleepy to get into your rhythm and grab those early SWS hours.

Another mechanism sleep and immune health are connected is through T-cell adhesion and the role of integrin. An effective T-cell response to a virus-infected cell is through its binding ability to the infected cell via integrin. In a study comparing those who slept all night vs those who stay awake, sleep up-regulated integrin activation compared to nocturnal wakefulness, an important mechanism sleeps exerts an immune-supportive effect(5).

Whether through inflammatory homeostasis, immune cell activation, or immune signaling, healthy sleep positively impacts the immune response in several ways and should therefore not be dismissed in its importance.

What exactly constitutes healthy sleep? It is not just the number of hours that dictate this. It has already been discussed how important time spent in deep restorative sleep is but simply focusing on the right number of hours it is a good starting point for most. Interestingly it has been demonstrated the benefits of sleep are a U-shaped curve. Those consistently sleeping <5 hour per night have increased risk of mortality while those sleeping > 9 hours per night also had an increased risk. It has been suggested those sleeping >9 often have comorbidities including heart disease, diabetes etc. The sweet spot for ideal sleep time appears to be between 7-8 hours per night(2). This once again brings us back to the basics we have heard over the years but now the mechanisms are being uncovered. Just because something seems to be simple, it does not always translate into action. In our busy world if sleep is not given the respect and priority it deserves, it is easy to fall short.

Stress
Likely everyone can relate to the relationship high stress may have on health.

Stress produces elevated levels of stress hormones such as adrenaline and cortisol. High levels of these hormones interfere with sleep, while at the same time, reduced sleep(<7hr/night) causes a fight or flight stress response, further elevating the stress hormones and further interfering with sleep. This becomes a perpetual escalating cycle; elevated stress creates poor sleep which then further perpetuates the stress response.

The concept of stress impacting one’s immune system health is not a new one, in fact in 200 AC Galenus suggested those suffering from melancholy were more likely to suffer with cancer than those who were positive and exposed to less stress. Further suggestion of the stress-immune connection came in the 1920’s when it was concluded that those living with stress had increased risk of developing tuberculosis. This idea continued to grow and in the late 1960’s researchers connected that those experiencing sudden, major stressful life changes had a greater probability of disease(6).

We have come a long way in understanding the mechanisms of how stress impacts immune health.

It is importat to recognize not all stress produces a negative immune outcome. An acute stress response can be lifesaving. We are inherently programmed to respond effectively to an immediate stress through our flight or fight response which can result in immune-boosting effects to fight off pathogens. Our well intentioned hypothalamic-pituitary-adrenal (HPA) access is meant to respond with various chemicals and hormones which after a period of time resolve and return to a healthy set point of homeostasis. Today we are living in a fast-paced treadmill of life where this acute stress response, meant for a short burst immediate threat, becomes ongoing and chronic, despite the lack of any true threat.

How a stressor is perceived by an individual is very influential. Perceived psychological stress can down-regulate parts of the cellular immune response. If fact, it has been shown both stress and depression can decrease cytotoxic T-cell and natural killer cells, affecting immune surveillance, potentially affecting the development and progression of tumours(7).

Academic stress has been an interest for many researchers. Studies have demonstrated exam stress in university students resulted in reduced natural killer cell activity which also correlated with a degree of loneliness. This type of stress also showed changes in antibody levels to the herpes virus. In both children and adults, depression and immunity studies have consistently shown reduced natural killer cell activity, thus impacting ones innate immune function(7). Chronic stress often results in depression, both of which negatively impact immune health.

Stress molecules such as corticosteroids and epinephrine are inversely related to the function of specific immune cells which have receptors to these molecules. Receptors to these have been found on both macrophages and lymphocytes, resulting in immunosuppression when these molecules are elevated(7). Growth hormone is another important hormone involved in immune regulation; chronic stress has been shown to inhibit growth hormone secretion(7).

The impact of stress may affect us before we ever knew what stress was.

Recent research has investigated the effects of stress in pregnant women on their fetuses. The stress response of the mom can be “transmitted to the fetus, resulting in permanent changes to the stress response system and health in the offspring”(8). Increased or decreased immune system activity from a mother’s constant stress response may become the new ‘normal’ for the offspring as a result of early life stress exposure (8).

Chronic stress via constant HPA activation affects hormones and chemical mediators that influence both the innate and acquire immune response. The effects on natural killer cells, macrophages, cytokines, and T cell activity has been demonstrated. Stress has also been demonstrated to increase DNA damage, increase mutations, and inhibit apoptosis, all of which may influence disease states such as cancer(7).

The good news is once we are aware, we can make change to better adapt and alter our course. Stress management should be a major priority for us all. Running on a ‘treadmill’ with little time to decompress can result in an aberrant immune response. Checking in with yourself to assess your stress levels and implementing strategies to manage this should be as routine as brushing your teeth.

REFERENCES:

1. Harvard Health Publishing. Harvard Medical School, April 6, (2020).
2. Cappuccio F., D’Elia L., Strazzullo P., Miller M. Sleep Duration and All-Cause Mortality: A Systemic Review and Meta-Analysis of Prospective Studies. Sleep, Vol 33, No 5 (2010).
3. Besedovsky L., Lange T., Born J., Sleep and Immune Function. Pflugers Arch. Jan; 463(1):121-137 (2012).
4. Irwin M., Opp M., Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity. Neuropsychopharmacology REVIEWS 42, 129-155 (2017).
5. Dimitrov S., Lange T., Gouttefangeas C., Jensen A., Szczepanski M., Lehnnolz J., Soekadar S., Rammensee HG., Born J., Besedovsky L. G-alpha-coupled receptor signaling and sleep regulated integrin activation in human antigen-specific T cells. Journal of Experimental Medicine. Feb 12, (2019).
6. Yaribeygi H., Panahi Y., Sahraei H, Johnston T., Sahebkar A. The Impact of Stress on Body Function: A Review. EXCLI Journal 16:1057-1072, (2017).
7. Reiche E., Nunee S., Morimoto H.Stress, depression, the immune system, and cancer. The Lancet Oncology Vol 5 October 2004.
8.  Moeser A. How Stress Makes Us Sick and Affects Immunity, Inflammation, Digestion. 2019

DR. VICTORIA COLEMAN is a 25-year veteran in health care delivery both clinically and in business development. A graduate of the Canadian Memorial Chiropractic College, Victoria has successfully run two wellness clinics delivering well health care from an integrative approach. Victoria is also a Certified in Functional Medicine and also holds a Master’s degree in Human Nutrition Encouraging proactive health care is a passion for Victoria along with a love for fitness.

This story was originally featured in the December 2020 edition of Chiropractic + Naturopathic Doctor, published online Nov. 30, 2020.