Serum IL-33 Level and IL-33, IL1RL1 Gene Polymorphisms in Asthma and Multiple Sclerosis Patients

Abstract

Background: Asthma is a chronic and complex inflammatory disease of the respiratory tract. Also, multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Against this background, IL-33 and IL1RL1 play a critical role in autoimmune and inflammatory disorders. Here, we explored the IL-33 serum level and two potential genetic variants in the IL33 gene and its receptor in Iranian asthma and MS patients. Results: The level of IL33 was significantly higher in asthma and MS patients compared to the control group (P< 0.001- P<0.001).The frequency distribution of the genotype in rs1342326 variant of IL-33 gene in patients with asthma, MS and healthy subjects was not significantly different (P>0.05). The frequency distribution of the genotype in rs10204137 variant of IL-33 gene in MS patients and healthy subjects was significantly different (p = 0.013). Methods: This study consisted of asthma (n=140) and MS patients (n=140), and healthy subjects (n=72). Genotyping was carried out in two genetic polymorphisms, rs1342326 variant of IL-33 and rs10204137SNP variant of IL-33 receptor genes, using High- Resolution Melt Real- Time PCR based method. The level of serum IL-33 was also measured using enzyme-linked immunosorbent assay method. Conclusion: Our findings demonstrated that asthma and MS patients had a higher level of IL-33, and IL-33 receptor genetic polymorphism was associated with MS. Further studies in a larger multicenter setting are needed to explore the value of this marker as a risk stratification biomarker.

Serum IL-5, POSTN and IL-33 levels in chronic rhinosinusitis with nasal polyposis correlate with clinical severity

“…Our present findings indicate elevated serum IL-33 protein levels in CRSwNP patients compared to control. Previous studies have also confirmed elevated IL-33 serum level in asthma patients [ 54 ].…”

Serum levels of epithelial‐derived mediators and interleukin‐4/interleukin‐13 signaling after bronchial challenge with Dermatophagoides pteronyssinus in patients with allergic asthma

“…It is released to alert the immune system by first‐line cells, such as tissue epithelial cells, following exposure to exogenous stimuli, including allergens . Importantly, high levels of serum IL‐33 and IL‐33 receptor genetic polymorphism were found in patients with multiple sclerosis, suggesting a relevant role of this cytokine in the pathogenesis of autoimmune disorders . However, our asthma patients were without history of autoimmune diseases that could influence the results.…”

Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time

“…In addition to REGN3500, etokimab represents a second clinically applicable anti-IL-33 antibody, whose suppressive in vivo effect on the function of IL-33 has successfully been validated in phase 1 and phase 2a clinical trials (143). As the alarmin IL-33 represents a well-established promotor of the bone marrow-tolung recruitment of ILC2s under inflammatory conditions and also serves as a key activating cytokine for pulmonary ILC2 pools (125,126), its antibody-mediated blockade can be expected to relevantly dampen the local involvement of ILC2s in the induction or maintenance of lung inflammation. Due to the rather broad expression profile of the IL-33 receptor ST2 on different immune cell subtypes, targeting IL-33 signaling does not represent an ILC2-specific strategy and can more be seen as a global approach to efficiently block type 2 immunity, including also marked inhibitory effects on lung infiltrating Th2 cells, eosinophils, mast cells and macrophages (144)(145)(146)(147)(148).…”

“…Experimental induction of allergic lung inflammation was found to result in a decreased ILC2 frequency in the bone marrow, while the number of pulmonary ILC2s increased subsequently, strongly implicating a targeted ILC2 migration from the bone marrow towards the inflamed tissue site ( 124 ). In this context, it was interesting to learn that the IL-1 family member IL-33, whose serum levels are markedly elevated in asthma patients ( 125 ), does not only function as a key activator of ILC2s in peripheral organs, but also crucially impacts on the inflammation-triggered egress of ILC2s from the bone marrow and their subsequent lung-directed hematogenous migration ( 126 ). Indeed, it could be demonstrated in vivo that the intravenous delivery of recombinant IL-33 into wild type mice resulted in a decreased total number of ILC2 precursor cells in the bone marrow, while the de novo generation of ILC2 precursor cells in the bone marrow turned out to be independent from IL-33 signaling ( 126 ).…”