The Importance of Sleep for the Immune System

Sleep is a major part of human life and is necessary for our survival, yet many of us consistently overlook its importance to the basic functions of our bodies.

Despite its significance, sleep often remains elusive to a large proportion of us. According to the Centers for Disease Control and Prevention (CDC), around one-third of adults and children under 14 and three-quarters of high schoolers in the U.S. don’t achieve the minimum amount of sleep recommended.

If you’ve ever suffered from a sleepless night, you’ll already know the more obvious impacts on the body the next day; you probably felt fatigued, lacking energy and motivation. Maybe you were irritable and found it difficult to focus on your day-to-day tasks. All in all, the lack of sleep has probably ruined your day. But did you know that your immune system is also significantly impacted?

In this blog, we delve into the specific effects of sleep on the immune response.

Sleep: The Best Medicine?

Rather than the passive state that it appears to be, sleep is, in fact, a highly dynamic and fundamental process that impacts various systems in the body. The vital nature of sleep was highlighted as far back as 1898, when physiologists Daddi and Tarozzi completely deprived dogs of sleep and found that the animals died after a mere 9–17 days (Bentivoglio and Grassi-Zucconi 1997).

Later experiments in rats observed that death following sleep deprivation was often associated with systemic infections by opportunistic pathogens, indicating a deficiency in the animals' immune response (Everson 1993, Everson and Toth 2000).

Using a mouse model of malaria blood-stage infection combined with rapid eye movement (REM) sleep deprivation, Fernandes et al. (2020) demonstrated that the increased susceptibility of REM-deficient mice to infection was linked to the impaired development of functional CD4+ T helper (Th) cells. In these animals, the differentiation of both Th1 cells, which induce cell-mediated immunity via the production of cytokines, and T follicular helper (Tfh) cells, which are essential for B cell maturation, was significantly compromised, allowing the infection to run rampant compared to in well-rested mice.   

Not only does sleep deprivation impact the adaptive immune response, but it also affects innate immunity. In studies in which humans were kept awake for over 40 hours, an increase in leukocyte populations, such as neutrophils and monocytes, has been reported, in addition to elevated levels of the cytokines IL-1β, IL-6, and TNFα (Mullington et al. 2013). As a result, continually getting insufficient sleep at night is often accompanied by chronic, low-grade inflammation.

Additionally, Sang et al. (2023) recently showed that significantly depriving mice of sleep (being awake 96% of the day) for four days resulted in severe inflammation. In fact, 80% of mice in this study died prematurely due to multiple organ dysfunction syndrome (MODS), with organ damage observed in the liver, spleen, lung, intestine, and kidneys. Further investigation revealed that this was caused by an accumulation of the immune mediator prostaglandin D₂, which subsequently triggered the overproduction of proinflammatory cytokines in what’s known as a “cytokine storm”.

So, now we know that the immune system is significantly disturbed by lack of sleep, but what impact does this have on the development and pathogenesis of disease?

Sleep it Off

Various studies show that consistently lacking sleep is, in fact, something to lose sleep over, as the impairment of the immune system leaves the body vulnerable to attacks on multiple fronts (Garbarino et al. 2021).

Research suggests that cancers, for example, breast, colorectal, and prostate cancer, are often associated with short sleep duration (Gapstur et al. 2014, Jiao et al. 2013, Kakizaki et al. 2008). A study that deprived mice of sleep for 18 hours a day for 21 days in a model of lung cancer found that sleep deprivation increased the growth rate of lung metastasis, which was accompanied by a reduction in natural killer (NK) and CD8+ T cells — the cells responsible for cytotoxic defence in the antitumor response — in the tumor microenvironment (De Lorenzo et al. 2015). This suggests a serious impairment of some of the most powerful players in the anticancer immune response.

Neurodegenerative diseases are also often connected to poor sleep. While many researchers hypothesize that altered sleep behavior is a consequence of these diseases, some have suggested a causative role in the development of neurodegeneration.

One such study examined sleep duration in a cohort of British adults that was established in 1985 and collected follow-up clinical data every 4–5 years for over 35 years. They found that persistent short sleep duration (six hours or fewer per night) at ages 50, 60, and 70 correlated with a 30% increased risk of developing dementia compared to those who achieved a normal sleep duration of around seven hours per night. These findings indicated that chronically lacking sleep in midlife could increase the risk of neurodegenerative issues in later years (Sabia et al. 2021).

Not only that, but sleep deprivation has also been associated with a 48% increase in the risk of coronary heart disease and a 15% increase in the risk of stroke, indicating a strong effect on the cardiovascular system (Cappuccio et al. 2011, Leng et al. 2015).

Interestingly, a recent study by Huynh et al. (2024) revealed that in mice and humans, myocardial infarction provoked the migration of monocytes to the brain, which led to the induction of deep sleep. This sleep proved to be beneficial to the recovery process by suppressing sympathetic stimulation of the heart and limiting inflammation, ultimately reducing the damage caused.

In general, while a sleepless night here and there is typically nothing to fret over, chronic sleep issues can have some serious consequences. For most of us, simply practicing good sleep hygiene, such as having a fixed wake-up and sleep schedule and following a nightly routine, can significantly improve sleep duration and quality and profoundly affect our overall health in the long term. So, with that in mind, we bid you a goodnight and sleep tight!