What it is:
It’s no coincidence that a few nights of poor sleep leaves us feeling under the weather. Or that age-old wisdom prescribes a good night’s rest when illness strikes. Sleep-immune crosstalk dictates that sleep is necessary in order for our immune system to perform optimally, but also, the state of our immune system can either help or hinder our sleep. For example, inflammation can lead to sleep disturbances.
Understanding how sleep relates to the body’s immune system allows one to appreciate how vital it is for protecting healthspan and lifespan, improving general quality of life, and staving off disease. In this article, we will also shed light on how poor immune function can create sleep problems, as well as what to do to reverse them.
The purported claims:
Maintaining a regular sleep schedule:
Prevents illness
Promotes rapid healing
Allows vaccines to work more effectively
Inflammation in the body can disturb sleep by:
Exacerbating sleep-disordered breathing
Leading to gut dysbiosis
Worsening autoimmune conditions
What the science says:
Immune System 101
The immune system protects the body from foreign invaders, such as microorganisms and toxic chemicals. It also removes cells that fall into disrepair at the end of their natural life or others that become mutated and cause problems, such as cancer cells.
The first line of defense against foreign invaders is the skin's physical border, along with other endothelial barriers, such as those lining the airways and gastrointestinal tract. The innate immune system kicks into gear if anything penetrates these barriers and ends up in the bloodstream. The defense comprises cells that dissolve and digest pathogens and signal the adaptive immune system that it must kick in and defend the body.
Unlike the frontline innate cells, which respond within minutes to hours, the adaptive immune system can take a few days to begin its job.
However, once it does, it responds precisely and effectively to each specific invader. It creates a memory of that pathogen so that it can be tackled much more quickly next time (what we refer to as "building immunity").
The immune system as a whole is comprised of many different cell types, signaling molecules, and proteins such as antibodies. Some immune cells destroy pathogens. For example, natural killer cells produce compounds that dissolve the cell membranes of foreign invaders. Other cells play vital roles by "mustering the troops" and calling other cells to migrate to an infected area. Cell-to-cell communication typically occurs through the production of chemical messengers, which are carried through the bloodstream. These markers of inflammation can be detected using blood tests and interpreted as signs of acute or chronic inflammation.
Pro-Inflammatory Biomarkers and Sleep
Cytokines are a common chemical messenger that either stimulates or reduces inflammation, depending on the type produced. In general, pro-inflammatory cytokines such as interleukins 1β and 6 (IL-1β and IL-6) are sleep-promoting, while anti-inflammatory cytokines (such as IL-4 and IL-10) tend to attenuate sleep.
Many studies have shown that short or fragmented sleep is associated with higher levels of these pro-inflammatory cytokines, with IL-1β , IL-6, and tumor necrosis factor-alpha (TNFα) among the most widely investigated. Interestingly, extended sleep (more than 9 or 10 hours per night) is also associated with significant inflammation. Unlike short sleep, which is likely the cause of the inflammatory response, long sleep is likely a symptom of an underlying health condition that may lead to fatigue and the need for prolonged sleep.
Some tissues in the body produce daily rhythms of these cytokines, with peaks typically occurring during nighttime sleep. From an evolutionary perspective, the natural rise of these compounds at night was a design feature to protect humans from disease when sleeping in confined spaces, thus providing a survival advantage.
Experimental sleep deprivation has been shown to suppress normal nocturnal peaks of these markers (such as IL-6), shifting the peaks to the daytime instead. This can cause sleepiness and fatigue, which has the potential to lower mood and drive a person to spend more time in bed.
Many of these pro-inflammatory cytokines can modulate sleep and the genes responsible for maintaining cell circadian rhythms. A prolonged irregular sleep schedule may lead to feelings of perpetual fatigue, with experiences of non-restorative, poor-quality sleep, and maybe even exacerbate autoimmune disorders.
It's also important to note that desynchronizing the normal daily rhythms of these inflammatory markers can lead to a general weakening of the immune response over time. The chronic elevation of the chemical messengers means in the event of an immune emergency (such as an infection), the immune cells don't respond appropriately.
Inflammation and Sleep Apnea
Measuring C-reactive protein (CRP) levels makes it possible to determine systemic inflammation. The liver produces CRP in response to peaks in cytokines such as IL-6. CRP is associated with a higher risk of cardiovascular disease and overall mortality and is elevated in obstructive sleep apnea (OSA) patients. Continuous positive airway pressure (CPAP) treatment has been shown to lower CRP levels, along with IL-6.
OSA is characterized by a collapsing of the airways during sleep, leading to frequent arousals throughout the night. Many of these micro-awakenings are not consciously registered by the person. Every time airflow is inhibited, a drop in blood oxygen levels occurs, known as intermittent hypoxia. This type of stress promotes inflammation in the body because sleep is continuously disturbed. Individuals with sleep apnea typically report excessive daytime sleepiness, headaches, snoring, and even waking up gasping. Many individuals also experience metabolic dysfunction (such as weight gain and insulin resistance) caused by this underlying pro-inflammatory response.
When sleep becomes fragmented, such as during sleep apnea, or other scenarios, such as having a noisy bed partner, this can lead to persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis. This is the primary stress-signaling highway in the body. Sleep fragmentation activates the sympathetic (“fight or flight”) branch of the autonomic nervous system, which releases epinephrine (also called adrenaline) into circulation. If this becomes chronic, it can suppress antiviral immune response genes and up-regulate inflammatory immune response genes. It can also induce glucocorticoid-resistant immune cells, leading to uncontrolled inflammation. Chronic inflammation is associated with depression and neurodegenerative conditions such as Alzheimer’s.
Vaccine Efficacy
In recent years, a connection has been theorized regarding the time of day a vaccine is administered and the antibody response in the following weeks. Specifically, studies showed men who received either a flu shot or hepatitis A vaccine in the morning experienced a better immune response than vaccines administered later in the day. More research is needed in different populations and greater numbers.
Melatonin is known for promoting sleep, but it is also a potent antioxidant associated with lower levels of pro-inflammatory cytokines, showing it to be essential for supporting vaccine efficacy. As an antioxidant, melatonin reduces the cell damage caused by oxidative stress. This lessens the burden on the immune system to perform “damage control” duties. Healthy melatonin secretion can be supported by reducing light exposure before bedtime, as melatonin is released in response to darkness at night.
How Inflammation Influences Sleep
Chronic inflammation can stem from environmental pollution, psychological stress, and chronic sleep loss. Toxic compounds from the environment require near-continuous activation of the immune system, which can exhaust the body’s resources and leave it in a pro-inflammatory state.
Individuals with asthma are susceptible to worsening symptoms when exposed to poor air quality. Irritation or airway inflammation can be particularly problematic if the person has OSA or another form of sleep-disordered breathing. Impaired breathing during sleep leads to fragmentation and drives systemic inflammation.
Another type of localized inflammation that can turn systemic occurs within the gut. Pro-inflammatory diets, such as those of highly processed foods, do not provide adequate nutrition and can lead to an unhealthy gut microbiome. Microorganisms associated with the typical “Western Diet,” rich in saturated fats and sugar and low in fiber, tend to produce compounds that can damage the gut lining and induce an inflammatory response. Many of these organisms are also associated with poor sleep and mood.
When sleep loss occurs due to chronic inflammation or unhealthy lifestyle choices, this can increase the risk of autoimmune conditions and exacerbate symptoms. Many people with rheumatoid arthritis report sleep problems, with higher pain levels the next day. It has also been shown that those with sleep disorders (other than sleep apnea) are at a greater risk of developing other autoimmune conditions, such as lupus and Sjögren’s syndrome.
Our take:
Sleep loss and inflammation are bidirectionally linked. Improvements in one tends to lead to improvements in the other and vice versa. The human body is remarkably resilient and can bounce back from acute infection or acute sleep loss. Still, chronic states of immune dysfunction or persistent poor sleep may require a more serious intervention.
Prioritizing your immune system's care may help you avoid frequent sickness. Prevent illness by prioritizing regular, quality sleep and a healthy lifestyle, including an anti-inflammatory diet. Regular exercise is also a potent immune system booster.
Will this benefit me?
Autoimmune disorders now affect approximately one in ten individuals. Environmental pollution, poor diet, sedentary lifestyles, sleep loss, and chronic stress are all factors in a constant, elevated immune response. In autoimmune conditions, the body's immune system turns on itself, mistakingly attacking healthy cells. While there is a genetic component to many of these disorders, you may stand a better chance of avoiding them or alleviating symptoms by engaging in healthy behaviors.
Still curious to try it? If you do, here's what to look out for:
Psychological stress is one of modern society's most pernicious contributors to immune system dysfunction. It directly drives inflammation in the body, but it also creates problems indirectly by keeping us awake at night, making us reach for unhealthy foods, and setting the stage for other harmful coping mechanisms (such as alcohol and addictive behaviors) that ultimately lead to worse health. Be mindful of your stress levels, and remember to take time to rest.
References & additional reading:
Adaptive vs innate immunity: https://www.ncbi.nlm.nih.gov/books/NBK279396
The Sleep-Immune Crosstalk: https://pubmed.ncbi.nlm.nih.gov/30920354/
Sleep Duration & Inflammation: https://pubmed.ncbi.nlm.nih.gov/26140821/
Sleep & Inflammation: https://pubmed.ncbi.nlm.nih.gov/31289370/
Sleep & Inflammation - A Bidirectional Link: https://pubmed.ncbi.nlm.nih.gov/37120163/
Neuroinflammation and sleep: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981587/
Sleep and vaccine efficacy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235253/
Morning vaccines better for men: https://pubmed.ncbi.nlm.nih.gov/18346041/
Melatonin and vaccine efficiency: https://pubmed.ncbi.nlm.nih.gov/34489630/
Proinflammatory diet and sleep: https://pubmed.ncbi.nlm.nih.gov/33071202/
Autoimmune disorders and sleep: https://pubmed.ncbi.nlm.nih.gov/31447842/
Stress and autoimmune diseases: https://pubmed.ncbi.nlm.nih.gov/29922828/
Rheumatoid arthritis and sleep: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(22)00311-3/fulltext
Sleep disorders and autoimmune conditions: https://pubmed.ncbi.nlm.nih.gov/25669189/
Autoimmune disorder statistics: https://www.ox.ac.uk/news/2023-05-06-autoimmune-disorders-found-affect-around-one-ten-people#:~:text=A new population-based study,about one in ten individuals.
Illustration made withbiorender.com
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