Sleep deprivation worsens inflammation and delays recovery in a mouse model of colitis

Abstract

Background and aim We recently showed that patients with inflammatory bowel disease (IBD) report significantly more sleep disturbances. To determine whether disrupted sleep can affect the severity of inflammation and the course of IBD, we used an animal model of colonic inflammation to determine the effects of acute and chronic intermittent sleep deprivation on the severity of colonic inflammation and tissue damage in colitis and recovery from this damage. Methods Acute sleep deprivation (ASD) consisted of 24 h of forced locomotor activity in a mechanical wheel rotating at a constant speed. Chronic intermittent sleep deprivation (CISD) consisted of an acute sleep deprivation episode, followed by additional sleep deprivation periods in the wheel for 6 h every other day throughout the 10 day study period. To induce colitis, mice were given 2% dextran sodium sulfate (DSS) in their daily drinking water for 7 days. The development and severity of colitis were monitored by measuring weight loss and tissue myeloperoxidase (MPO) activity daily and colon histology scores 10 days after initiation of colitis. Results ASD or CISD did not cause colonic inflammation in vehicle-treated mice. Changes in daily body weight, tissue MPO levels and colon histopathology score were similar between mice that were sleep deprived and controls. Daily DSS ingestion caused colitis in mice. ASD worsened colonic inflammation: tissue MPO levels in ASD/DSS-treated mice were significantly higher than in DSS-treated mice that were not sleep deprived. However, the worsening of colonic inflammation by ASD was not enough to exacerbate clinical manifestations of colitis such as weight loss. In contrast, the deleterious effects of CISD were severe enough to cause worsening of histological and clinical manifestations of colitis. The deleterious effects of sleep deprivation on severity of colitis appeared to be due to both increased colonic inflammation and a decrease in the ability of mice to recover from DSS-induced colonic injury. Conclusion Both acute and chronic intermittent sleep deprivation exacerbate colonic inflammation. Thus, sleep deprivation could be an environmental trigger that predisposes IBD patients to develop flare ups and a more severe disease course. These results provide a scientific rationale to conduct an interventional trial to determine whether improvement in sleep patterns will prevent IBD flare ups, modify the disease course, and improve quality of life.

A population-based study of fatigue and sleep difficulties in inflammatory bowel disease

“…A recent experimental study using an animal model of colitis found that acute and intermittent sleep deprivation patterns aggravated inflammation and slowed recovery, with some evidence of a 'dose' response. 15 Stress has been found to alter the release of pro-inflammatory mediators, and increase intestinal permeability, which can contribute to intestinal inflammation. 47 Finally, a novel communication pathway between the immune system and the brain has been described, 48 suggesting that inflammation in chronic disease may cause fatigue through monocyte infiltration in the brain.…”

“…13 Sleep disturbances have been associated with exacerbation of symptoms such as pain and fatigue in multiple chronic inflammatory conditions as well as worsening disease course. 14,15 Studies on fatigue in IBD have primarily relied on smaller samples (n<100), tertiary clinic recruitment, and patients with IBD in remission, 6,16 thereby considering only part of the spectrum of IBD presentation. The aim of this study was to evaluate fatigue and its related parameters more comprehensively, considering sleep quality, psychological factors, and biological indicators of inflammation and serum hemoglobin (Hg) levels simultaneously, in order to clarify their presentation and relationships in IBD.…”

Chronic fatigue is more prevalent in patients with inflammatory bowel disease than in healthy controls

“…40 There is further evidence that sleep deprivation may increase gastrointestinal symptom activity. 40,41 A possible explanation for this finding may be that altered sleep is an indication of increasing disease activity. Indeed, IBD patients have reported in previous studies to relate their disturbed sleep with disease activity.…”

Fragmented Sleep Enhances Postoperative Neuroinflammation but Not Cognitive Dysfunction

“…12,13 SF by itself can also induce activation of inflammatory mechanisms, more specifically tumor necrosis factor (TNF)-α-dependent pathways, which propagate the engagement of the innate immune system. 14,15 Polysomnographic studies have revealed profound sleep disruption in ICU patients with decreases in total sleep time, altered sleep architecture, and severe SF. 16,17 We posited that the combination of SF and surgery would enhance the neuroinflammatory response produced either alone or that the combination results in exacerbated cognitive impairment.…”