Sleep 'intimately tied' to increased inflammation, worse disease course in IMIDs
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Experimental studies indicate that sleep loss can lead to elevated concentrations of proinflammatory cytokines and enhance the perception of pain among patients with immune-mediated inflammatory diseases, according to a speaker here.
“Sleep disturbance seems to be a key feature of many of immune-mediated inflammatory diseases, and what drives those sleep disturbances are likely multifaceted,” Aric A. Prather, PhD, an associate professor of psychiatry and behavioral sciences at the University of California, San Francisco, told attendees at the 2021 Interdisciplinary Autoimmune Summit. “Certainly, disease severity can impact sleep; experiences of pain and discomfort can make it hard to sleep. There is also evidence that it’s bidirectional — that when people have poor sleep, they may report higher severity of their disease just because our pain thresholds change.”
“Sleep has been related to depression, which certainly can contribute,” he added. “There is some good evidence linking sleep disturbance and elevated levels of systemic inflammation, as well as pro-inflammatory mediators following stimulation with various antigens or mitogens. Finally, of course, there are medications that can impact sleep disturbance. The one we think of most commonly is high-dose glucocorticoid, but there are likely others that can mess around with the sleep system.”
According to Prather, sleep disturbance is rampant throughout populations of patients with IMIDs. He cited studies from Abad et al., published in Sleep Medicine Reviews in 2008, and by Palagini et al., in Lupus in 2016, that found that 54% to 70% of patients with rheumatoid arthritis, and 56% to 80% of those with systemic lupus, experience sleep disturbance or insomnia. In addition, between 36% to 81.8% of those with psoriasis demonstrate sleep apnea, he added.
Sleep is “intimately tied” in a “bidirectional” relationship with the immune system, including the pathways that regulate inflammation, Prather said. Epidemiologic studies support cross-sectional and longitudinal associations between sleep and markers of inflammation, while experimental studies support the effects of acute sleep loss on increased concentrations of inflammation-inducing cytokines, he added.
“On the whole, when we deprive people of sleep, the impact on the inflammatory system is fairly mixed — in some studies it does show an increase in some of these pro-inflammatory mediators that are associated with IMIDs, but in other cases there aren’t any differences,” Prather said. “The studies are fairly different from each other. They use different sleep-loss paradigms, whether it’s partial sleep loss or a long-term sleep-loss of days, which likely has an impact on the consistency of the findings.”
In one study — from Irwin et al., published in the Archives of Internal Medicine, in 2006 — 30 individuals underwent 3 days of baseline sleep in the laboratory followed by partial sleep deprivation, where they were allowed to sleep from 3 a.m. to 7 a.m. In addition, the researchers collected blood samples in the morning during both sleep paradigms and analyzed them for the presence of inflammatory mediators. According to the researchers, the partial sleep deprivation paradigm was associated with an increase in the gene expression of interleukin-6 and TNF alpha.
In addition, although the experimental sleep loss data are mixed, the data linking patient-reported loss disturbance and inflammation levels are not, Prather said.
“On the whole, looking at IL-6, there is a positive relationship across the various studies when aggregated, so that individuals in studies where they report higher sleep disturbances, those individuals also tended to have higher levels of systemic inflammation,” he said.
Regarding the possibility that treating inflammation may improve sleep, Prather stated that several biologics are available to treat IMIDs that target proinflammatory cytokines. However, few studies have tested the effects of these drugs on sleep and sleep quality.
“Sleep disturbances are common in these populations of patients with IMIDs,” Prather said. “There are absolutely multiple causes of sleep disturbance, many of them bidirectionally linked to sleep. Sleep disturbance can lead to increased levels of inflammation, which may contribute to disease course, and there is a small but fairly intriguing set of data on the benefit of cytokine antagonists or inhibitors to improve sleep, but, again, these are only preliminary.”
He added: “There is absolutely a need for more rigorous, well-powered designs, and it’s my hope that both researchers and companies developing these medications will engage in the sleep community to more adequately test the power of these associations and effects.”
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Prather AA. Understanding the Role of Sleep in IMIDs. Presented at: Interdisciplinary Autoimmune Summit. April 15-18, 2021 (virtual meeting).
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