Introduction
Interleukin 33 (IL-33) is a pro-inflammatory cytokine that has been implicated in the pathophysiology of inflammatory bowel disease (IBD), ulcerative colitis (UC) in particular. IL-33 as a cytokine and an alarmin might evoke systemic inflammation, which could have ramifications for the functioning of the central nervous system, contributing to mood and sleep disorders. Disruptions in IL-33 concentration are well known to occur in the course of numerous psychiatric disorders as well as obstructive sleep apnea, a condition characterized by chronic low-grade inflammation and sleep fragmentation. To date, however, this protein has not been studied in relation to insomnia or poor sleep quality, frequently comorbid to chronic inflammatory and psychiatric diseases.
Aims & Methods
The study aimed to compare serum IL-33 concentrations of IBD patients and healthy controls as well as evaluate the association between the expression level of this interleukin, depression, sleep quality, and insomnia. IBD patients (n=81) and healthy controls (HC=44) were recruited. Harvey-Bradshaw index or partial Mayo were applied in the assessment of clinical disease activity for Crohn’s disease (CD) or UC respectively. Venous blood samples as well as questionnaires: Beck Depression Inventory (BDI), Epworth sleepiness scale (ESS), Athens Insomnia Scale (AIS), and Pittsburgh Sleep Quality Index (PSQI) were collected. Human IL-33 High Sensitivity Magnetic Luminex Performance Assay was used for the analysis of serum IL-33 protein concentration according to the manufacturer’s protocol. Fluorescence measurements were taken with MAGPIX, Luminex. The study has been funded by National Science Centre, Poland (2018/31/N/NZ5/03715).
Results
No differences were noted regarding IL-33 concentrations, sleep, or psychological variables between IBD patients and HC, except for sleep efficiency, which was higher in HC (p=0.004). Only in the IBD group, a positive correlation between IL-33 concentration and BDI, PSQI, and AIS (R=0.521, p=0.003; R=0.458, p=0.01; R=0.40, p=0.03), as well as negative one with sleep efficiency (R=-0.475, p=0.008) was noted. IBD individuals with high scores on ESS or PSQI (ESS>10, PSQI>5) had elevated IL-33 serum level compared to IBD patients without sleep problems (IL-33 concentration [pg/ml]: 53.385 (30.070-313.020) vs 18.795 (11.790-26.175), P=0.01 for PSQI; 270.900 (156.225-438.680) vs 21.840 (11.870-47.720), P=0.006 for ESS). IL-33 concentrations and questionnaire scores were comparable in patients with different disease activity. As for IBD types, in the CD, but not the UC group, IL-33 was positively correlated with the severity of depression symptoms and poor sleep quality (R=0.581, p=0.02; R=0.531, p=0.03) and negatively with sleep efficiency (R=-0.667, p=0.005).
Conclusion
IL-33 might be associated with mood and sleep disorders in IBD. It could exert its effect by promoting systemic and neuroinflammation, thus negatively affecting the well-being of IBD patients. Further research on the subject of changes in mental health of IBD patients in the context of anti-inflammatory or immunosuppressive treatment would be valuable.