Sleep deprivation worsens inflammation and delays recovery in a mouse model of colitis
Received 15 August 2008; received in revised form 7 December 2008; accepted 11 December 2008.
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 24h 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 6h every other day throughout the 10day study period. To induce colitis, mice were given 2% dextran sodium sulfate (DSS) in their daily drinking water for 7days. The development and severity of colitis were monitored by measuring weight loss and tissue myeloperoxidase (MPO) activity daily and colon histology scores 10days 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.
aDepartment of Internal Medicine, Division of Digestive Disease and Nutrition, Rush University Medical Center, 1725 W. Harrison, Suite 206, Chicago, IL 60612, USA
bDepartment of Pharmacology and Molecular Biophysics & Physiology, Rush University Medical Center, Chicago, IL 60612, USA
cDepartment of Pathology, Rush University Medical Center, Chicago, IL 60612, USA
dCenter for Sleep & Circadian Biology, Department of Neurobiology & Physiology, Northwestern University, Evanston, IL 60208, USA
ABSTRACT