Tag Archives: excessive daytime sleepiness

Does sleep protect us from illness?

We have all heard that getting more sleep decrease the likelihood of getting sick?  On the flip side, we know that illness commonly makes us tired but does sleep help us recover quicker?  By examining the medical literature, this blog post will attempt to answer these questions.

It is no secret that sleep rejuvenates our bodies and is essential for proper body functions.  For many years, the effect of sleep on the immune system was largely criticized and considered far-fetched. However, in recent years, many studies have investigated the relationship between a good night’s sleep and the effect it has on the immune system of the body. Although the literature does not define an exact mechanism for enhanced immunity associated with sleep, the evidence of a connection is quite clear.

The Immune System

Before discussing the studies, a primer on immunity is needed.  Our immune system protects our bodies from a disease and infection. It is triggered by a harmful stimulus or stress, which causes increased production and growth of the immune cells.  This system consists of a range of immune cells that protect the body from harmful antigens. The major cellular components are white blood cells (or leukocytes). Some of the white blood cells also produce protein based substances called cytokines which play an integral part in the immune response.

Cytokines are further classified in many subtypes. One of the types of classification divides cytokines into pro-inflammatory cytokines that include Interleukin-1 and Tissue Necrosis Factor (TNF), and anti-inflammatory cytokines that include Interleukin-4, Interleukin-13 and Interleukin-10.

All of the mentioned immune components can be affected by sleep and sleep loss.  In our discussion of the relationship between sleep and immunity, we will explore these cell types and mediators.

The Effect of Sleep on the Immune System

Now that we have discussed the different types of immune cells, we will consider how the individual component is affected by a good night’s sleep.

In a study conducted by Uthgennannt [2] and Schoolmann, 13 healthy men were asked to spend two nights in the sleep laboratory. Lights out was 11 pm and the subjects were allowed to sleep for 3.5 hours. They were then asked to stay awake till 7 am, when blood was sampled. In another condition, the subjects were asked to stay awake between 11 pm and 3 am and then permitted to sleep for 3.5 hours. Blood was sampled every 30 minutes.  In the first condition, when the subjects were allowed to sleep at night, there was a decreased amount of pro-inflammatory cytokines, TNF-alpha and Interleukin-1, while opposite results were observed for those who stayed awake.

In other studies, the serum level of Interleukin-7  which is involved in the maturation and migration of immature T-lymphocytes was observed to increase during the Slow Wave stage of sleep, with a subsequent rise in naïve T-lymphocytes themselves. [1]

Another study conducted by Matsumoto [5], on a 24-hour wake period, demonstrated a marked decrease in cytotoxic NK cells, important cells of inflammation.  In addition, there was a decrease in anti-inflammatory cytokines such as Interleukin-10.

Although the levels of cytokines fluctuate, and the exact pattern is pretty complex; in a nutshell, the main pro-inflammatory cytokines decrease during nocturnal sleep (usually in Slow Wave Sleep stage), whereas the levels of T-lymphocytes and cytokines that are involved in the growth and differentiation of T-lymphocyte as well as those that take part in adaptive immunity (more later) increased. This reflects that sleep, indeed, has a positive effect in boosting the immunity of our bodies since it allows for some cells and cytokines to peak levels while keeping other components at bay.

Another aspect of immunity that is theorized to enhance during sleep is the formation of immunologic memory. Normally when a person is infected by a particular pathogen, immune cells memorize the response.  By forming antigen specific antibodies, the body reacts more rapidly to any subsequent attacks by the same pathogen. Studies have revealed that subjects who stayed awake after a hepatitis A vaccine shot demonstrated lower levels of antigen-specific antibody titers compared to those who received the vaccine and slept regularly [1]. This proves that not only does sleep help in enhancing the cellular elements of the immune system, but it also helps in the formation of immunologic memory.

Adaptive Immunity vs. Innate Immunity

Numerous studies have established that sleep has a direct effect on adaptive immunity, and less so on innate immunity.

Innate immunity involves the protection against a foreign antigen by the body’s defense mechanisms that do not include the antigen-specific immune cells. These defense barriers include the skin, chemicals in the body and cytotoxic immune cells. Adaptive immunity is more complex and encompasses the reaction of antigen-specific immune cells which includes recognizing the antigen, releasing a cascade of immune cellular components and mediators, and finally removing the pathogen.

Research on the decreased levels of Interleukin-6 during sleep which acts as both a pro-inflammatory and anti-inflammatory agent and takes part in innate immunity suggests that innate immune response is less affected during sleep. Similarly, the serum level of interferon-alpha that plays a core role in the innate immune response against viral infection also declined during sleep. On the other hand, Interleukin-7, an important mediator of adaptive immunity, showed a marked increase during sleep. [6]

The Effect of Prolonged Wakefulness on the Immune System

While inflammation is an early response to infection, an inflammatory response unchecked can be detrimental. Several studies have looked at the relationship between sleep deprivation and immunity. The results of these studies were fairly consistent that the levels of the immune cells were impacted by sleep quantity.

Blood samples from individuals subjected to prolonged wakefulness showed a marked increase in inflammatory mediators such as interleukin-6 levels, pro-inflammatory cytokines, TNF-alpha, interleukin-1 and C-reactive protein [7] An increase in these pro-inflammatory cells made the subjects more vulnerable to stress. In addition, the elevated levels of these inflammatory markers is associated with cardiovascular disease and type 2 diabetes. [1]

Does Sleep Decrease the Likelihood of Getting Sick?

Although the relationship between sleep and immunity is still being researched, many studies indicate a strong relationship between a proper sleep/wake cycle and improved immunity of the body.  There is little doubt that a good night’s sleep can decrease the likelihood of getting sick.

 

References

  1. Besedovsky, Luciana, Tanja Lange, and Jan Born. “Sleep and immune function.” Pflugers Archiv. Springer-Verlag, Jan. 2012.
  2. Uthgenannt, D., D. Schoolmann, R. Pietrowsky, H. L. Fehm, and J. Born. “Effects of sleep on the production of cytokines in humans.” Psychosomatic medicine. U.S. National Library of Medicine, n.d.
  3. Sarosh J. Motivala, Michael R. Irwin. “Current Directions in Psychological Science”Vol 16, Issue 1, pp. 21 – 25, June 24. 2016
  4. Dinarello, C. A. “Proinflammatory cytokines.” Chest. U.S. National Library of Medicine, Aug. 2000.
  5. Matsumoto Y, Mishima K, Satoh K, Tozawa T, Mishima Y, Shimizu T, Hishikawa Y. Total sleep deprivation induces an acute and transient increase in NK cell activity in healthy young volunteers.Sleep.2001;24:804–809.
  6. Dimitrov S, Lange T, Nohroudi K, Born J. Number and function of circulating human antigen presenting cells regulated by sleep.Sleep.2007;30:401–411
  7. Meier-Ewert HK, Ridker PM, Rifai N, Regan MM, Price NJ, Dinges DF, Mullington JM. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk.J Am Coll Cardiol.2004;43:678–683.

It’s good to breathe

Obstructive sleep apnea can be quite dangerous when not treated.  Restricted airflow which occurs repetitively in individuals with sleep apnea stresses the body in several ways.  We know that people who suffer from obstructive sleep apnea have a higher risk of high blood pressure, stroke, irregular heart rhythms, elevated blood glucose levels, car accidents and even sudden cardiac death.  In addition, people with sleep apnea often feel tired, complain of non-restorative sleep and have a poor quality of life.  Having untreated sleep apnea does not necessarily mean that an individual will ever suffer these ailments, but it does raise the risk.   The more severe the sleep apnea, the higher the likelihood of ever suffering from one of these entities.

Untreated sleep apnea results in these ill effects for two main reasons.  First of all, the oxygen levels dip which stresses the body. The second reason is that sleep apnea results in fragmented and poor quality sleep.

When people don’t breath well at night,  oxygen levels repetitively dip resulting in bodily stress.  As most people are aware, our body tissues need adequate oxygen for optimal function.  It can thought of as a stress test every night.  When a person’s upper airways narrow, airflow is limited and oxygen levels drop.    Most people’s oxygen levels remain at 97-100%.  Associated with apnea events, oxygen levels drop by at least 3%.  It is not uncommon for oxygen levels to drop even further.  Individuals with severe sleep apnea commonly have drops of their oxygen levels into the 70-80% range.  I have seen patient’s with oxygen levels dipping into the 50s%!     When the tissues are starved of adequate oxygen, the risk of heart attack and stroke increases.  The sympathetic nervous system is activated which results in elevated blood pressures with frequent surges in blood pressure and heart rate.   In addition, inflammatory mediators are released which can further damage tissues.

Sleep apnea also results in fragmented  and poor quality sleep.  After a good night’s sleep, a person should feel refreshed and ready for a full day’s activities.  Optimal sleep should last 7-8 hours in adults during which a person cycles through stages of sleep.   There should be 3-4 sleep cycles during which a person transitions from light sleep, to deep sleep and then into REM sleep.  We call this sleep architecture.  Each stage of sleep is associated with important bodily functions like memory consolidation, hormone secretion and clearing of accumulated waste products.   If an individual’s sleep is disrupted by sleep apnea, sleep architecture becomes fragmented and the full benefits of sleep are not achieved.  The breathing events associated with sleep apnea frequently cause arousals.  Essentially, arousals are ‘brain awakenings’ which disrupt sleep architecture.    For example, a person with moderate or severe sleep apnea will commonly have more than 15 arousals per hours which prevents them from entering the restorative stages of sleep such as deep sleep.  This is why a patient with sleep apnea will commonly state that they never feel like they slept.

Indeed, it is good to breathe.  This article explains why obstructive sleep apnea leads to an increased risk of cardiovascular problems, as well as excessive daytime sleepiness.