IL-33/ST2 immunobiology in coronary artery disease: A systematic review and meta-analysis

Abstract

The IL-33/ST2 axis is reported to be controversially associated with coronary artery disease (CAD). A systematic review of the association between the IL-33/ST2 axis and CAD revealed that IL-33/ST2 plays a protective role in CAD and serum sST2 and IL-33 levels are increased in patients with cardiovascular disease. Therefore, the association of IL-33/ST2 single nucleotide polymorphisms (SNPs) with CAD prevalence, prognosis, and risk factors was assessed by performing a meta-analysis. Through a literature search of relevant articles in various databases using the relevant keywords, seven studies were included in the analysis. The meta-analysis showed that the IL-33/ST2 axis was associated with increased CAD risk [pooled odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.13–1.20]. Gene subgroup analysis showed a close association of IL1RL1 (OR = 1.25, 95% CI: 1.20–1.30; I2 = 85.9%; p = 0.000) and IL1RAcP (OR = 1.42, 95% CI: 1.26–1.60; I2 = 27.1%; p = 0.203) with increased CAD risk. However, the association for the IL-33 gene was not statistically significant. SNPs rs7044343 (T), rs10435816 (G), rs11792633 (C) in IL-33 gene were associated with a protective effect in CAD. However, rs7025417 (T) in IL-33, rs11685424 (G) in IL1RL1, rs950880 (A) in sST2, and rs4624606 (A) in IL1RAcP were related to increased CAD risk. Overall, polymorphisms in IL-33/ST2 axis components were associated with increased CAD risk. These results may help identify key features of IL-33/ST2 immunobiology in CAD along with potential treatment strategies to lower disease burden.

Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19

“…Focusing on the single nucleotide polymorphisms (SNPs) of IL-33 , we discovered a significant inverse association between IL-33 SNP rs3939286 and COVID-19 severity, which meant that carriers of the minor genotype were found to be protected from developing more severe forms of COVID-19. While the role of IL-33 SNPs in viral infections, particularly COVID-19, remains largely unexplored, previous studies have indicated a protective effect of this SNP in other diseases, such as rheumatoid arthritis and cardiovascular conditions [ 29 , 30 ]. It is plausible to suggest that rs3939286 may play a role in regulating IL-33 production and, subsequently, lowering the risk of developing severe disease in these conditions.…”

The role of IL-33 in depression: a systematic review and meta-analysis

“…A recent study on mouse depression showed (49) that the IL-33 gene is associated with mouse social stress (SS), and changes in mouse coronary blood flow, and that there is a link between MDD and coronary heart disease. Our prior study demonstrated that IL-33's immune regulatory role in CAD regulation is inconsistent, which may be due to the different biological roles of IL-33 as a cytokine and transcription factor (52). Hence, we hypothesize that IL-33's biological activity in acting as both a cytokine and transcription factor can influence the regulation of depression.…”

The Impact of Cytokines in Coronary Atherosclerotic Plaque: Current Therapeutic Approaches

“…A subsequent study stressed the prognostic significance of IL-33 in patients after revascularized acute coronary syndrome, with higher levels indicating a higher disease complexity and poorer 1-year prognosis [76]. It should also be stated that although the IL-33/ST2 axis may be related to coronary atherosclerosis, the various gene single nucleotide polymorphisms may modify this association, as suggested by a recently reported systematic review and meta-analysis [77]. Other than its role in atherosclerosis, IL-33 exerts a protective effect in most infectious settings, by assisting the clearance of the causal microorganism [78].…”