Sleep, Cytokines, and Inflammation

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The pro-inflammatory consequences of the lack of sleep

So many of us struggle with sleep, and have difficulties getting enough rest in terms of both time and quality. Whether it be due to nighttime awakenings to care for children or loved ones, a demanding job, or a health condition, sleep problems can cause trouble in many different aspects of our health. We often hear that sleep is healing and restorative, and know this intuitively, but what is the research that supports this?

Effects of sleep deprivation

One way we can learn about the benefits we derive from sleep is from sleep deprivation studies. Sleep deprivation has been shown to be associated with worse performance on cognitive tasks and motor performance,[1],[2] depression, feelings of burnout, decrease in feelings of empathy,[3] increased vulnerability to infection,[4] weight gain,[5] and decreased ability to balance blood sugar levels.[6] In fact, moderate sleep deprivation has been shown to impair both mental and physical performance as much as a blood alcohol content of 0.1%, which in most locations exceeds the legal limit.[7] These findings of course become issues of significant concern in jobs where sleep deprivation is common such as medical residents, emergency room physicians, and military personnel. Although we don’t all fit into these categories, that does not alleviate the importance that healthy sleep has for us all.

The pro-inflammatory effects of diminished sleep

Many inflammatory markers and hormones are impacted by sleep and the lack thereof. Many of these have fluctuate throughout the day, and as such the impact of sleep is not surprising.[8] The night-time decrease in the stress hormone cortisol and increase in the calming antioxidant melatonin is well known to be important for quality sleep, but immune and inflammatory mediators such as interleukin (IL)-6 also normally increase at night and induce fatigue.[9]

In fact, moderate sleep deprivation has been shown to impair both mental and physical performance as much as a blood alcohol content of 0.1%, which in most locations exceeds the legal limit.

Markers of inflammation such as C-reactive protein (CRP), which does not vary through the day in healthy subjects,[10] have been shown to be increased with both acute total and short-term partial sleep deprivation.[11] Even more surprisingly, the increases in CRP extend beyond the days with diminished sleep. CRP levels have been shown to continue to be high with two days of sleep recovery (8 hours/night) immediately after the sleep restriction.[12] Other measured inflammatory signals (IL-1β, IL-6, and IL-17) also were increased with sleep restriction, with IL-17 continuing to remain elevated after two days of recovery sleep as well. In another study, prolonged acute sleep deprivation (34 hours) was shown to increase levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α).[13] The circadian rhythm of the secretion of IL-6 and TNF-α has been observed to be shifted in individuals with chronic insomnia,[14] a factor which may be important to consider with interventions directed at inflammation in addition to other supportive therapies.

The blood-brain barrier, sleep, and stress

If these factors alone are not alarming enough to cause us to retreat back to bed for an extra hour of sleep, this one may be. The integrity of the blood-brain barrier, which is crucial for protection of the central nervous system from circulatory proteins and toxins that may contribute to neuroinflammation and damage, also is affected by sleep restriction.[15] The low-grade inflammation associated with sleep loss and the previously mentioned increases in inflammatory markers may lead to the altered function of the brain cells and tight junction proteins, weakening the blood-brain barrier.[16]

The integrity of the blood-brain barrier, which is crucial for protection of the central nervous system from circulatory proteins and toxins that may contribute to neuroinflammation and damage, also is affected by sleep restriction.

Disruption of the tight junctions of the blood-brain barrier may contribute to numerous neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and more.[17] Stress also increases permeability of the blood-brain barrier via the release of corticotropin-releasing hormone (CRH), a hormone produced by the body when it perceives stress.[18] Elevations in CRH and cortisol, a stress hormone CRH stimulates, are also associated with disrupted sleep,[19] perpetuating the trouble.

The benefits of a nap

Although the reports from patients and self-assessment on the benefits of napping may be quite varied, positive effects generally have been shown. A recent review surveying the impact of a scheduled nap in populations such as emergency medical services personnel and similar shift workers found that a nap had moderate yet significant positive effects on sleepiness both during and at the end of a shift.[20] In placebo-controlled settings, a nap has been shown to have beneficial effects on sleep-deprivation symptoms as well as biochemical parameters after a night of total sleep loss. After taking a two-hour nap, subjects experienced significantly less sleepiness, with trends towards improvements in psychomotor vigilance tasks (tasks like pressing a button every time a light flashes).[21] Biochemically, the two-hour nap was found to reverse the changes to cortisol and the inflammatory cytokine IL-6 caused by one night of sleep loss as well.

Regardless of status of health or disease, the physiological changes experienced with a loss of sleep, especially on a prolonged basis, can have significant impact, shedding light on the importance of sleep for all. Melatonin, the hormone our body produces that promotes sleep, also is available as a supplement and has been used clinically in populations ranging from the young to old for this purpose.

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