Is Poor Sleep Pummeling the Immune System in ME/CFS and Fibromyalgia? A Vicious Circle Examined by Cort Johnson

Most people with chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) know the consequences of poor sleep - the fatigue and pain, the difficulty concentrating, the irritability, and more. Sleep is when our body rejuvenates itself; no sleep - no rejuvenation. Given how important sleep is to our health, it's no surprise that poor sleep is the first symptom many ME/CFS and FM doctors focus on in.

The effects of poor sleep go beyond just feeling bad, though. It turns out that poor sleep can have significant effects on our immune system - effects, interestingly, which are similar to what's been found in the immune systems of people with ME/CFS and FM.

There's no evidence yet that ME/CFS and FM are sleep disorders - that the problems ME/CFS and FM patients face are caused by poor sleep - but depriving the body of sleep can cause one immunologically, at least, look like someone with these diseases.

In Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective Michael Irwin begins his review on sleep and immunology by noting the "explosion" in our understanding of the role sleep plays in health over the past decade. First, Irwin asserts that sleep studies are not effective in diagnosing insomnia or sleep disturbances other than sleep apnea.

Far more effective, in his opinion, than a one or two-night sleep study is a home-based sleep actigraph "study" which estimates sleep patterns and circadian rhythms over time and is coupled with a sleep diary.

Irwin points out that the diagnosis of insomnia in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is based solely on patient reports of difficulties going to sleep, maintaining sleep, having non-restorative sleep (common in ME/CFS), and problems with daytime functioning (fatigue, falling asleep, need to nap). (Problems with daytime functioning are required for an insomnia diagnosis).

Several effective sleep questionnaires exist including the Insomnia Severity Index, which assesses sleep quality, fatigue, psychological symptoms, and quality of life, and the Pittsburgh Sleep Quality Index, a 19-item self-report questionnaire that evaluates seven clinically derived domains of sleep difficulties (i.e., quality, latency, duration, habitual efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction).

Assessing Your Sleep Quality

The Stress Response and Sleep

Studies show the fight or flight response is chronically activated in ME/CFS and FM

The immune system is vast and incredibly complex and has it's own extensive set of regulatory factors, but it itself is regulated by two other systems, the HPA axis and the sympathetic nervous system. Both are involved in the stress response and both are effected in ME/CFS and FM.

One - the HPA axis - is blunted in ME/CFS while the other - the sympathetic nervous system - is over-activated. Poor sleep, it turns out activates both systems. While studies indicate that the HPA axis is blunted (low salivary cortisol) in the morning in ME/CFS patients, the sympathetic nervous system (SNS) is whirring away at night (when it should be relaxing) in both FM and ME/CFS. (Having our "fight or flight" system acting up at night is probably not the best recipe for sleep.)

Sympathetic nervous system activation, in fact, was the only factor in one Australian study which explained the poor sleep in ME/CFS. The authors of a recent FM/autonomic nervous system study went so far as to suggest that going to sleep with FM was equivalent to undergoing a stress test (!).

Heart rates, muscle sympathetic nervous activation, and other evidence of an activated sympathetic nervous system response made sleep anything but restful for FM patients. The authors proposed sleep problems could be a heart of fibromyalgia.

The Immune System and Sleep

Pathogens love it when we don’t get good sleep!

Many questions have involved the roles pathogens play in ME/CFS and FM. That's intriguing given the almost universally poor sleep found in the disorders and the role studies indicate that sleep plays priming the immune systems pump to fight off invaders.

During sleep pathogen fighting immune cells move to the lymph nodes where they search for evidence of pathogens. If pathogens are present those immune cells mount a furious (and metabolically expensive) immune response.

Metabolism is a big issue in ME/CFS right now but guess what? Poor sleep also appears to interfere with producing the metabolic reserves our immune cells need to fight off infections. We often think of inflammation in negative terms but the pro-inflammatory cytokines our immune cells produce are necessary to fight off invaders.

Reductions of a key pro-inflammatory cytokine called IL-6 during poor sleep hampers our immune system's ability to destroy pathogens.

Getting your circadian rhythms (altered sleep and wake times) out of whack isn't helping. Insomnia and/or altered sleep patterns such as very late bedtimes) appears to cause deficits in two hormones (growth hormone (GH) and prolactin) produced during early sleep which enhance T-cell activity and promote pathogen defense.

The immunological problems that poor sleep causes at night bleed into the daytime. Chronic sleep deprivation is associated with increased daytime levels of several immune and endothelial factors ((IL-6, TNF) and endothelial markers (E-selectin, sICAM-1) that are associated with chronic inflammation. One study found IL-6 levels were flipped in sleep-deprived people; i.e. they were low at night (thereby hampering their pathogen-fighting ability) and high during the day (adding to inflammation).

The situation may be even worse if a sleep-deprived person is fighting off an infection.  One study found skyrocketing levels of damaging pro-inflammatory cytokines when sleep-deprived people were given a toxin (LPS) associated with infections suggesting sleep deprivation resulted in higher levels of inflammation.

In general, women seem to have gotten the short end of the stick with regard to immune issues and it's no different with sleep. Women appear to be more susceptible than men to inflammation that occurs as the result of poor sleep; it's women, not men, who show elevations of pro-inflammatory cytokines the day after getting less than eight hours of sleep. (Men show elevations of pro-inflammatory cytokines after getting less than six hours of sleep).

Many people with ME/CFS/FM get too little sleep but sleeping more than normal, it turns out, also has its costs. People sleeping much longer than normal tend to show the same kinds of elevations of pro-inflammatory cytokines as do people who get too little sleep.

The C-reactive Protein Sleep, ME/CFS and Fibromyalgia Connection

Inflammation - Increased levels of the inflammatory marker, C-reactive protein (CRP), are increasingly being associated with sleep disturbance. The CRP - sleep connection is intriguing given Jarred Younger's preliminary finding of increased C-reactive protein (CRP) levels in a subset of ME/CFS patients, and a recent finding of increased CRP in FM.

*See Early Results Suggest Two Radically Different Immune Subsets Present in Chronic Fatigue Syndrome (ME/CFS)

Those findings might not be so surprising. Ten days or so of partial sleep deprivation in healthy controls caused "robust" increases in CRP levels. The CRP-poor sleep connection is so robust that simply scoring above five on the Pittsburg Sleep Quality Index (PSQI >5) strongly suggests that your CRP levels are elevated.

A huge nurses study (n=10,908) found that non-restorative sleep - probably the most common sleep issue in ME/CFS/FM - was associated with increased CRP levels even in these healthy individuals.

Innate Immune Response - The early or innate immune response (NK cells, neutrophils, macrophages, dendritic cells and others) has long been thought to play a special role in ME/CFS and plays a major role in the inflammation associated with infection.

NK cell activity hits a low during sleep but then begins to rise. That the rise is blunted in people with poor sleep probably comes as no surprise to NK cell-challenged ME/CFS patients. Depression is associated with low NK functioning as well and having poor sleep increases your risk of being depressed twofold.

Plus, for reasons that are not understood, poor sleep appears to trigger stress and depression-initiated reductions in NK cell activity; i.e. if you're having poor sleep and are under considerable stress or are depressed - your NK cells may be punking out when you need them most and are confronted with a pathogen.

We know that having a chronic illness increases one’s chances of becoming depressed markedly, but so does poor sleep. Irwin reports that having insomnia for over a year increases your risk of becoming depressed 14-fold. That finding is leading some of the more progressive psychologists to focus on preventing or ameliorating sleep problems.

Vaccines - Sleep disturbance also induces a shift toward a type-2 immune response often seen in ME/CFS and in allergic and autoimmune diseases. Just one poor night's sleep the night before a person is given a vaccine is enough to markedly reduce the effectiveness of that vaccine.

A study showing just how frighteningly malleable the immune system can be to stressors such as poor sleep found that a 50% reduction in the effectiveness of an influenza vaccine persisted over a year. Even after three doses of the vaccine and a booster shot were given adults getting fewer than six hours of sleep a night still received less protection from a hepatitis B vaccination than normal.

The common cold, of course, is no joke to some people with chronic fatigue syndrome (ME/CFS) and FM when it lingers and lingers. Studies suggest that poor and fragmented sleep - which is, of course, common in ME/CFS/FM - significantly increases one's susceptibility to the common cold. If you're catching a lot of colds or if they linger and linger, poor sleep could be one reason why.

What To Do?

Stress reduction techniques may help with sleep in chronic fatigue syndrome (ME/CFS) and fibromyalgia

OK - so poor sleep places a big hurt on our immune system's effectiveness. What to do about it?  No studies, unfortunately, have examined the effect of sleep drugs on immune factors so we're not going to go there.

Several studies have, however, assessed the efficacy of stress reduction therapies. Dr. Irwin notes reports that practices such as cognitive behavioral therapy, Tai Chia, and yoga which tamp down sympathetic nervous system hyper-arousal can help improve immune functioning. Tai chi has even been found to improve vaccine effectiveness and reduce inflammation.

Other studies point to the ability of mindfulness-based meditations and/or yoga to reduce the cytokine levels and pro-inflammatory gene expression caused by poor sleep.  One remarkable study showed a 50% reduction in CRP levels in insomnia patients after a year of cognitive behavioral therapy.

Poor sleep, then, doesn't just make you feel tired and irritable; it takes a pretty good whack at your immune system, as well.  Getting better sleep through better sleep hygiene, supplements (melatonin), calming botanicals (valerian root, L-theanine, passifloraMelissa, Scutellaria, etc.), stress reduction techniques (meditation, mindfulness, meditation), and sleep medications might give your immune system a much-needed boost.

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