mRNA expression of NLRP3 and IL1B in inflammatory bowel diseases: a systematic review and meta-analysis

Abstract

Background: Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. Clinical studies of IBD robustly show elevated interleukin 1β (IL-1β) levels in intestinal tissue, implicating the NLR family pyrin domain containing 3 (NLRP3) inflammasome, which controls IL-1β secretion in myeloid cells. In this study, we aimed to ground potential NLRP3 involvement in IBD in molecular evidence from human studies. Methods: This systematic review and meta-analysis investigated NLRP3 and IL1B mRNA expression in biopsies of intestinal tissue and cells isolated from unstimulated blood of IBD patients compared to healthy controls (HCs), using standardized mean differences (SMD) [95% confidence interval (CI)], p-values and heterogeneity (I2), and a meta-correlation of the meta-analyses. Results: A systematic search in Medline and Embase identified 2218 records, with 30 studies describing 33 separate datasets meeting inclusion criteria. Meta-analysis revealed consistently higher NLRP3 and IL1B mRNA expression in intestinal tissue of IBD patients (24 datasets, n = 3912; NLRP3: SMD = 0.53 [0.36, 0.70], p < 0.001, I²=66%; IL1B: SMD = 0.95 [0.66, 1.24], p < 0.001, I²=89%). In blood, IL1B expression was significantly elevated (9 datasets, n = 1921; SMD = 0.20 [0.06, 0.33], p = 0.003, I²=15%), while NLRP3 expression showed no significant increase (SMD = 0.12 [-0.16, 0.40], p = 0.40, I²=78%). SMDs of NLRP3 and IL1B in tissue strongly and positively correlated with each other (rho = 0.854 [0.687, 0.935], p < 0.001). Conclusion: We found upregulation of both NLRP3 and IL1B mRNA in intestinal tissue of IBD patients, which highly correlated across 24 studies, reinforcing the role of the NLRP3 inflammasome in IBD and its potential as a therapeutic target.