The meta-analysis results indicated that any allele frequencies of the IL-18 polymorphisms (A-607C, G-137C and A-105C) was not associated with asthma risk (p>0.05).
The ATP/P2X7 axis of dendritic cells (DCs) mediates the activation of NLRP3 inflammasome and promotes secretion of interleukin (IL)-1β and IL-18 to induce T helper (Th) 2, Th17 differentiation in the pathogenesis of asthma.
Our data clearly indicate that the role of IL-18 in asthma is very likely to be determined by balance of IL-18/IL-18BP/IL-18R expression in inflammatory cells.
In parallel, BALF concentrations of soluble VEGFR1 and IL-18 were significantly reduced in severe asthmatics in vivo and inversely correlated with angiogenesis.Activin-A is overexpressed and has anti-angiogenic effects in vitro that are not propagated in vivo, where reduced basal expression of its receptors is observed particularly in severe asthma.
In addition, recent results indicate that the TLR-2 → NLRP3 → caspase-1 → IL-18 axis is critical to H. pylori-specific immune regulation conferring protection against allergen-induced asthma and inflammatory bowel disease in murine models.
The aim of this study was to investigate the association of IL-18-607C/A promoter polymorphism with asthma and whether this polymorphism influenced the severity of asthma in affected children.
IL10 rs1800896, IFNG rs2430561, and IL18rs1872387 polymorphims and their associations with asthma and allergy were studied in 135 preschool-aged children hospitalized for bronchiolitis at age 0-6 months.
In conclusion, polymorphisms of the IL-18 gene promoter at -607C/A and -137G/C were associated with allergic rhinitis in bronchial asthma, indicating that polymorphisms of the IL-18 gene promoter at -607C/A and -137G/C differentially affect the pathogenesis of asthma and allergic rhinitis.
We genotyped single nucleotide polymorphisms (SNPs): -105/rs28665122 in SELS or SEPS1 (selenoprotein), three single nucleotide polymorphisms in IL18 (-105/rs360717, +183/rs5744292 and +1467/rs574456) and R501X/rs61816761 in FLG, the major locus associated with atopic dermatitis and predisposing to asthma, in a minimum of 6743 T1D cases and 7864 controls.
Multimarker analysis identified TGFB1, IL1RL1, the gene encoding IL-18 receptor 1 (IL18R1), and DPP10 as the genes most significantly associated with asthma.
There was weak evidence to implicate the following: IL13, IFNGR2, EDN1, and VDR in asthma; IL18, TBXA2R, IFNGR2, and VDR in atopy; TLR9, TBXA2R, VDR, NOD2, and STAT6 in airway hyperresponsiveness; TLR10, IFNGR2, STAT6, VDR, and NPSR1 in atopic asthma.
Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 -137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66-1.94).