[Effects of allergens on the expression levels of interleukin 18, interleukin 18 binding protein a and interleukin 18 receptor α in the blood monocyte subtypes of patients with allergic asthma].

Abstract

Objective: To assess the effects of allergens on interleukin-18 (IL-18), IL-18 binding protein a (IL-18BPa), and IL-18 receptor α (IL-18Rα) expression levels in different monocyte subtypes of the peripheral blood samples of allergic asthma (AA) patients, and the correlations between the percentage of IL-18⁺classical monocytes and plasma levels of pro-inflammatory cytokines. Methods: A cross-sectional study. Blood samples were collected from 28 healthy controls and 33 patients experiencing acute attack of AA based on a positive skin prick test of Henan Provincial People's Hospital from February 2023 to April 2024. Flow cytometry was used to assess the effects of allergens on IL-18, IL-18BPa, and IL-18Rα expression levels in the classical, intermediate, and non-classical monocytes of the peripheral blood samples of AA patients. Kruskal-Wallis test and Pairwise test were used to analyze statistical significance between groups. Plasma tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) levels were estimated using Bioplex assays. Pearson correlation test was used to determine the association between the percentage of IL-18⁺classical monocytes and the plasma levels of IL-1β and TNF-α. Results: Compared with healthy controls, the percentages of classical and non-classical monocytes in the peripheral blood of AA patients were reduced by 20.2% (Z=-3.89, P<0.001) and 45.8% (Z=-4.01, P<0.001), respectively. Allergens increased the percentages of classical, intermediate, and non-classical monocytes in AA patients in vitro by 13.1%-61.5% (all P<0.05). Compared with healthy controls, the percentages of IL-18 expression in classical monocytes of AA patients was elevated by 1.08-fold (Z=-6.40, P<0.001), whereas the percentages of IL-18 expression in intermediate and non-classical monocytes were reduced by 52.7% (Z=-6.40, P<0.001) and 3.23% (Z=-3.13, P=0.001), respectively. Allergens upregulated IL-18 expression by 16.4%-67.8% in the classical and intermediate monocytes of AA patients (all P<0.05). Compared with healthy controls, IL-18BPa expression level was lower in the three monocyte subtypes of AA patients (all P<0.05). However, allergens upregulated IL-18BPa expression by 8.9% and 13.3% in the classical monocytes (both P<0.05). Compared with healthy controls, IL-18Rα expression was elevated by 1.29-fold in the classical monocytes of AA patients (Z=-6.40, P<0.001). Allergens upregulated IL-18Rα expression by 17.6%-39.2% in the three monocyte subtypes of AA patients (all P<0.05). Plasma levels of IL-1β and TNF-α in the AA patients were increased compared to those in healthy controls (all P<0.001), and correlated with the percentage of IL-18⁺classical monocytes (r=0.451, 0.714; both P<0.05). Conclusions: Allergens may participate in the inflammatory response of AA by inducing the differentiation of monocytes and the expression levels of IL-18, IL-18BPa and IL-18Rα in different blood monocytes subtypes. Classical monocytes are the potential source of elevated plasma IL-18 level in AA patients.