The level of IL-18 was significantly elevated in lymphocyte cultures with SEB stimulation in AD vs. control (p<0.05) and without SEB in AD vs. control (p<0.05).
The decrease in molar concentration ratio of plasma IL-18BP/IL-18 and allergen-induced upregulated expression of IL-18 and IL-18R in skin mast cells of the patients with eczema suggests that anti-IL-18 including IL-18BP therapy may be useful for the treatment of eczema.
This study was designed to investigate the association of the IL-18 gene SNPs (-137 G/C [rs187238], and -140 C/G [rs360721]) with AR and AD, as well as their relations to the diseases' severity.
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.
We showed that the rs438421 polymorphism in the IL-12RB1 (TT) gene and the rs2066446 polymorphism in the IL-12RB2 (AA) gene had a significant interaction to develop the ADe phenotype (allergic type of AD), and those individuals with the risk alleles, TT/AA/CC (IL-12RB1/IL-12RB2/IL-18), have more than a 10-fold increased risk to develop ADe.
Among various transgenic and knockout mouse models, the IL-18-transgenic mouse is one of the closest available mouse models of human AD, although the onset of the AD-like lesions in the IL-18-transgenic mice is such a late event.
These results strongly suggest that the development of AD in cathepsin E-deficient mice is initiated by systemic accumulation of IL-18 and IL-1beta, mainly due to their reduced turnover rates.
Because IL-18 directly stimulates T cells and mast cells to release AD-associated molecules, Th2 cytokines, and histamine, we investigated the capacity of IL-18 to induce AD-like inflammatory skin disease by analyzing KIL-18Tg and KCASP1Tg, which skin-specifically overexpress IL-18 and caspase-1, respectively.
The aim of this study was to elucidate the role of monocytes and soluble factors, with special focus on IL-18, in the pathogenesis of atopic dermatitis (AD).