OBJECTIVE: Oral diseases act as a silent epidemic, and the pathogenetic role of interleukin-33/suppression of tumorigenicity-2 axis (IL-33/ST2) remains unclear due to a lack of literature. This review has attempted to highlight the importance of this axis in oral diseases, which may be helpful in developing therapeutic modalities required to halt disease progression.
METHODS: A thorough search was conducted using various databases. Original research articles that assessed both IL-33 and ST2 levels in oral diseases using different techniques were included in the review. The risk of bias for each study was analyzed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and Review Manager 5.4 was used to output the results.
RESULTS: In the qualitative data synthesis we included 13 published articles. The most commonly used method was serum estimation, while methods with optimistic results were saliva, real-time quantitative polymerase chain reaction and immunohistochemistry. The predominant mechanism of action was nuclear factor kappa B signaling and type 2 immune response. However, salivary gland epithelial cell activation, activation of mast cells, type 1 immune response, and upregulated angiogenesis are crucial in mediating IL-33/ST2 signaling in oral diseases.
CONCLUSIONS: Accumulating evidence demonstrates that the IL-33/ST2 axis is a fundamental pathogenetic mechanism of oral diseases of inflammatory, autoimmune, or neoplastic origin.

Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis remains an incurable disease, the management of MS predominantly focuses on reducing relapses and decelerating the progression of both physical and cognitive decline. The continuous autoimmune process modulated by cytokines seems to be a vital contributing factor to the development and relapse of multiple sclerosis. This review sought to summarize the role of selected interleukins in the pathogenesis and advancement of MS. Patients with MS in the active disease phase seem to exhibit an increased serum level of IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 and IL-33 compared to healthy controls and patients in remission, while IL-10 appears to have a beneficial impact in preventing the progression of the disease. Despite being usually associated with proinflammatory activity, several studies have additionally recognized a neuroprotective role of IL-13, IL-22 and IL-33. Moreover, selected gene polymorphisms of IL-2R, IL-4, IL-6, IL-13 and IL-22 were identified as a possible risk factor related to MS development. Treatment strategies of multiple sclerosis that either target or utilize these cytokines seem rather promising, but more comprehensive research is necessary to gain a clearer understanding of how these cytokines precisely affect MS development and progression.

The aim of this review is to specify new potential reliable and non-invasive methods for the diagnosis of biliary atresia (BA) that could shorten the way to diagnose BA, and finally the surgical treatment. Apart from the biomarkers that have been proven helpful and are used nowadays in neonatal wards, there are several new potential biomarkers that researchers have found to be helpful in the diagnosis of biliary atresia. Circulating microRNAs, matrix metalloproteinase-7, stool proteins, interleukin-33, Th17-associated cytokines, urinary metabolomics, anti-smooth muscle antibodies, heat shock proteins 90 and positive biliary epithelial cells CD56 are among those presented in this summary. These markers may play a new significant role in BA diagnosis. The described methods include Nomogram, Circulating microRNAs (miRNAs), Matrix metalloproteinase-7 (MMP-7), Stool proteins, Interleukin-33 (IL-33), Th17-associated cytokines, Alpha-aminoadipic acid and N-acetyl-d-mannosamine in urine, Anti-smooth muscle antibodies (ASMA), Heat shock proteins 90 (HSP90), Positive biliary epithelial cells CD56.

The intestinal tract is the largest immune organ in the human body, comprising a complex network of immune cells and epithelial cells that perform a variety of functions such as nutrient absorption, digestion, and waste excretion. Maintenance of homeostasis and effective responses to injury in the colonic epithelium are crucial for maintaining homeostasis between these two cell types. The onset and perpetuation of gut inflammation, characterizing inflammatory bowel diseases (IBD), are triggered by constitutive dysregulation of cytokine production. IL-33 is a newly characterized cytokine that has emerged as a critical modulator of inflammatory disorders. IL-33 is constitutively expressed in the nuclei of different cell types such as endothelial, epithelial, and fibroblast-like cells. Upon tissue damage or pathogen encounter, IL-33 is released as an alarmin and signals through a heterodimer receptor that consists of serum Stimulation-2 (ST2) and IL-1 receptor accessory protein (IL-1RAcP). IL-33 has the ability to induce Th2 cytokine production and enhance both Th1 and Th2, as well as Th17 immune responses. Exogenous administration of IL-33 in mice caused pathological changes in most mucosal tissues such as the lung and the gastrointestinal (GI) tract associated with increased production of type 2 cytokines and chemokines. In vivo and in vitro, primary studies have exhibited that IL-33 can activate Th2 cells, mast cells, or basophils to produce type 2 cytokines such as IL-4, IL-5, and IL-13. Moreover, several novel cell populations, collectively referred to as \"type 2 innate lymphoid cells\" were identified as being IL-33 responsive and are thought to be important for initiating type 2 immunity. Nevertheless, the underlying mechanisms by which IL-33 promotes type 2 immunity in the GI tract remain to be fully understood. Recently, it has been discovered that IL-33 plays important roles in regulatory immune responses. Highly suppressive ST2 + FoxP3+ Tregs subsets regulated by IL-33 were identified in several tissues, including lymphoid organs, gut, lung, and adipose tissues. This review aims to comprehensively summarize the current knowledge on IL-33\'s role in the gut immune system, its crosstalk, and regulation. The article will provide insights into the potential applications of IL-33-based therapies in the treatment of gut inflammatory disorders.

The aim of this systematic review was to investigate whether phase angle (PhA) of bioelectrical impedance is associated with inflammatory markers in cardiovascular diseases (CVDs).
A search was performed in the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American Caribbean Health Sciences Literature (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Scopus; and in the gray literature up to January 2022. Studies with individuals with CVDs were included, to evaluate the association between PhA and the inflammatory markers interleukin (IL)-6, IL-10, IL-18, IL-1β, IL-33, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), toll-like receptor (TLR) 2, TLR 4, nuclear factor κB, pathogen-associated molecular pattern molecules, lipopolysaccharides, interferon-γ-inducing factor, and JAK STAT.
We identified 755 articles and, after an eligibility analysis, 5 studies were included. The inflammatory markers investigated in the studies were CRP, TNF-α, and IL-33. In patients with CVDs, PhA was negatively associated with CRP and TNF-α in 80% and 100% of the studies, respectively.
The present results suggested that PhA is inversely associated with inflammatory markers in individuals with CVDs, and its clinical use is encouraged for better therapeutic planning.

The IL-33/ST2 signaling pathway has potential relevance for clinical identification and treatment of Alzheimer\'s disease (AD). Here, eight databases (including CNKI, Wanfang, SinoMed, VIP, PubMed, Cochrane library, Embase and Web of Science) were employed to search for studies on IL-33/ST2 signaling pathway and its association with AD. Totally, 15 articles were included, of which 5 studies investigated the connection between IL-33 gene polymorphisms and AD, 4 studies explored the serum IL-33 and sST2 levels in patients with AD and Mild cognitive impairment (MCI), and the exact mechanisms underlying IL-33/ST2 signaling pathway in AD were explored in 6 studies. Then, the RevMan 5.4 software was used for meta-analysis, and the related studies were systematically reviewed. The results of the meta-analysis showed that serum IL-33 levels were higher in patients with AD and MCI than in healthy controls (HC), with serum IL-33 levels in AD patients significantly higher than in MCI patients (SMD = 0.26, 95 % CI: 0.02, 0.51; P = 0.04). Compared with HC, the sST2 level was significantly higher in AD patients (SMD = 1.23, 95 % CI: 0.93, 1.53; P < 0.00001) and tended to elevate in patients with MCI. The systematic review indicated that there is a significant relationship between IL-33 gene polymorphisms and susceptibility to AD; The IL-33/ST2 signaling pathway may be one of the future treatment targets for AD. Our study provides evidence to prove that serum IL-33 and sST2 have potential clinical application value as biomarkers for identifying AD.

BACKGROUND: This study evaluated the association between peptidyl arginine deiminase type IV (PADI4) and interleukin 33 (IL-33) with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA).
METHODS: We searched the PubMed, Web of Science, Embase and Cochrane Library databases to retrieve articles published up to January 20, 2023. Stata/SE 17.0 (College Station, TX) software was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The cohort study, case-control study focusing on the PADI4, IL-33 polymorphism, and SLE, JIA were retrieved. The data included basic information of each study and the genotypes and allele frequencies.
RESULTS: Studies in PADI4 rs2240340 = 2 and 3 IL-33(rs1891385 = 3, rs10975498 = 2, rs1929992 = 4) were found in 6 articles. Overall, only the IL-33 rs1891385 show significant association between SLE in all 5 models. The results were OR (95% CI) = 1.528 (1.312, 1.778), P = .000 in Allele model (C vs A), OR (95% CI) =1.473 (1.092, 1.988), P = .000 in Dominant model (CC + CA vs AA), 2.302 (1.583, 3.349), P = .000 in Recessive model (CC vs CA + AA), 2.711 (1.845, 3.983), P = .000 in Homozygote model (CC vs AA), 5.568 (3.943, 7.863), P = .000 in Heterozygote model (CA vs AA). PADI4 rs2240340, IL-33 rs10975498, IL-33 rs1929992 were not found to be association with the risk of SLE and JIA. In gene model, statistically significant association was found between IL-33 rs1891385 and SLE in sensitivity analysis. Egger\'s publication bias plot showed there was no publication bias (P = .165). Only in recessive model the heterogeneity test was significant (I2 = 57.9%, P ≤ .093) of IL-33 rs1891385.
CONCLUSIONS: The current study suggests that in all 5 model, IL-33 rs1891385 polymorphism may be associated with genetic susceptibility to SLE. There was unclear association found between PADI4 rs2240340, IL-33 rs10975498, and IL-33 rs1929992 polymorphisms and SLE and JIA. Due to the limitations of included studies and the risk of heterogeneity, additional research is required to confirm our findings.
UNASSIGNED: CRD42023391268.

A meta-analysis of the association between IL-33 and these diseases is lacking, and we aimed to perform a meta-analysis of the association between IL-33 and systemic sclerosis (SSc). We searched relevant papers through PubMed (via Medline), Embase (via Ovid), and the Cochrane Library through May 18th, 2022. Odds ratios (ORs) and weighted mean differences (WMDs) were estimated using a random effect model. A total of 8 papers were included in our meta-analysis. The pooled results showed that SSc patients had significantly higher serum IL-33 levels than healthy controls (HCs) (SMD = 0.64; 95% CI = 0.34, 0.93; P < 0.001); early SSc patients had significantly higher serum IL-33 levels than late SSc patients (SMD = 1.04; 95% CI = 0.28, 1.80; P = 0.007). However, no significant difference was observed between limited cutaneous SSc and diffuse cutaneous SSc (SMD =  - 0.35; 95% CI =  - 0.76, 0.06; P = 0.094). Our meta-analysis provided important evidence for the use of IL-33 in therapeutic strategies for fibrotic disorders.

Interleukin-33 (IL-33), a member of the IL-1 family, is an alarmin cytokine with crucial roles in tissue homeostasis and repair, type 2 immunity, allergic and non-allergic inflammation, viral infection, and cancer. IL-33 is abundant in the nuclei of tissue-derived cells, including endothelial cells from blood vessels, epithelial cells from barrier tissues, and fibroblastic stromal cells from various tissues. IL-33 is released upon cell damage or tissue injury and activates Myd88-dependent signaling pathways in cells expressing the ST2 (IL-1RL1) receptor. Analysis of patient samples and studies in murine models support an important role of IL-33/ST2 signaling in allergic inflammation in different tissues (lung, nasopharynx, skin) and diseases (asthma, chronic rhinosinusitis, allergic rhinitis, atopic dermatitis). IL33 and IL1RL1/ST2 are among the most highly replicated susceptibility loci for asthma. However, the IL-33/ST2 pathway is also important in non-allergic inflammation. Indeed, targets of IL-33 include immune cells involved in both type 2 and type 1 immunity and regulatory responses, such as group 2 innate lymphoid cells (ILC2s), mast cells, regulatory T cells (Tregs), Th2 cells, basophils, eosinophils, macrophages, dendritic cells (DCs), neutrophils, Th1 cells, CD8 T cells, NK and iNKT cells. In the main part of this review, we discuss the basic biology of the IL-33 protein (molecular characteristics, nuclear localization, cellular sources in vivo), and its mechanisms of release, and bioactive forms in various contexts. Importantly, we alert the scientific community to the problems of specificity of IL-33 reagents, we explain why studies without specificity controls with IL-33-deficient cells are misleading to the field and lead to unnecessary controversy, and we make recommendations to generate reliable results. In the final part, we review the genetic and environmental regulation of IL-33 in allergic airway inflammation and asthma, and we highlight recent studies showing clinical efficacy of anti-IL-33 antibodies in asthma and chronic obstructive pulmonary disease (COPD).

IL-33 is a newly discovered cytokine displaying pleiotropic localizations and functions. More specifically, it also functions as an alarmin, following its release from cells undergoing cell death or necrosis, to alert the innate immune system. The role of IL-33 has been underlined in several inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE). The expressions of IL-33 as well as its receptor, ST2, are significantly upregulated in SLE patients and in patients with lupus nephritis. This review discusses the involvement of IL-33 in the pathology of SLE.