August 29th, 2017, Cort Johnson Source: http://simmaronresearch.com/2017/08/ sleep-reduced-immunity-vicious-circle-mecfsfibromyalgia/
Ed note: This article was sourced from ANZMES Meeting Place 130 (Summer 2017) and has been abridged.
The immune system is vast and incredibly complex and has its 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 affected in ME/CFS and fibromyalgia (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. The HPA axis is generally thought to be blunted, not activated, in the morning in ME/CFS patients, but the sympathetic nervous system (SNS), on the other hand, is whirring away at night (when it should be relaxing) in both ME/CFS and FM. 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. In fact, the authors proposed sleep problems could be at the heart of FM.
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 recent studies indicate that sleep plays in priming the immune system’s 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.
Disrupted circadian rhythms (sleep/wake cycles) aren’t doing you any good either. Having insomnia or altered sleep patterns (e.g. 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 defence. That suggests that anyone with an altered circadian rhythm might want to do their best to get to bed earlier.
While pro-inflammatory cytokine production at night primes the immune system to fight off pathogens, the daytime is a different story. 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 actually became flipped in sleep-deprived people; they were low at night (thereby hampering their pathogenfighting 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. Those damaging cytokines did not show up in healthy people. That suggested that, besides the infection they
probably weren’t doing too well at fighting off, sleep-deprived people now had inflammation to deal with.
As often happens, women seem to be more affected by immune issues, and it’s no different with sleep. Women appear to be more susceptible than men to inflammation that occurs as a result of poor sleep; women show elevations of pro-inflammatory cytokines the day after getting less than 8 hours of sleep; men show elevations of pro-inflammatory cytokines after getting less than 6 hours of sleep.
Many people with ME/CFS/FM get too little sleep but sleeping more than normal, it turns out, is not good either. 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
CRP is associated with a variety of inflammatory states resulting from infection, cancer and stress. 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 CRP levels in a subset of ME/CFS patients, and a recent finding of increased CRP in fibromyalgia (FM).
Those findings might not be so surprising. Ten days or so of partial sleep deprivation in healthy controls caused ‘robust’ increases in CRP levels. In fact, the CRP – poor sleep connection is so robust that simply scoring above 5 on the Pittsburgh Sleep Quality Index (PSQI) strongly suggests that your CRP levels are elevated.
The PSQI is a 19-item self-report questionnaire that evaluates 7 clinically derived domains of sleep difficulties, i.e. quality, latency, duration, habitual efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. A huge nurses study (n=10,908) found that nonrestorative sleep – probably the most common sleep issue in ME/CFS/FM – was associated with increased CRP levels, even in these healthy individuals.
The early or innate immune response has long been thought to play a special role in
ME/CFS. This immune response involving NK cells, neutrophils, macrophages and others constitutes the immune system’s first defence against pathogens.
NK cell activity normally hits a low during sleep but then begins to rise. This rise is blunted in sleepdeprived ME/CFS/FM people. Immune cells called monocytes/macrophages, also involved in the early immune response, play a key role in producing chronic inflammation.
ME/CFS isn’t the only condition associated with NK cell problems; depression is as well, and having poor sleep increases your risk of being depressed two-fold. Plus, for reasons not yet understood, if you are having poor sleep and are under considerable stress or are depressed, it’s likely that your NK cells will be considerably less effective when called on to defend the body from invaders.
We know that having a chronic illness increases one’s chances of becoming depressed markedly, but so does poor sleep. In fact Michael 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.
Sleep disturbance also indicates a shift towards 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. Studies also suggest that poor and fragmented sleep – which is 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 for some time, poor sleep could be one reason why. What To Do?
So poor sleep has a major effect on our immune system’s effectiveness. No studies, unfortunately, have examined the effect of sleep drugs on immune factors.
However, several studies have assessed the efficacy of stress reduction therapies. Dr Irwin notes reports that practices such as cognitive behavioural therapy, Tai Chi and yoga, which dampen down sympathetic nervous system hyper-arousal, can help improve immune function. 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 behavioural therapy.
Poor sleep therefore doesn’t just make you feel tired and irritable; it hits your immune system as well.
Getting better sleep through improved sleep hygiene, supplements (melatonin), calming botanicals (valerian root, L-theanine, passiflora, melissa, scutellaria etc), stress reduction techniques (meditation, mindfulness), and sleep medications might just give your immune system a boost.
* Michael R. Irwin. Annu Rev Psychol. 2015January 3;66:143-172.doi:10.1146/