Altered expression of IL-18 binding protein and IL-18 receptor in basophils and mast cells of asthma patients

Abstract

IL-18 is likely to contribute to asthma. However, little is known regarding the role of IL-18 binding protein (BP) and IL-18 receptor (R) in asthma. Because the action of IL-18 in the body is regulated by IL-18BP and mast cells and basophils are key cell types involved in asthma, we investigated the expression of IL-18, IL-18BP and IL-18R in basophils and mast cells using flow cytometry and a mouse asthma model. We found that among basophils, approximately 53% and 51% were IL-18+, 85% and 81% were IL-18BP+ basophils, and 19.8% and 8.6% were IL-18R+ in healthy control (HC) and asthmatic blood, respectively. The allergens tested had little effect on the expression of IL-18 and related factors. Only 3.5%, 14.3% and 2.4% of dispersed mast cells expressed IL-18, IL-18BP and IL-18R, respectively, in asthmatic sputum. In a mouse asthma model, OVA-sensitized mice exhibited decreased IL-18BP+ but increased IL-18R+ basophils in their blood. IL-18 increased the number of basophils but eliminated IL-18BP+ basophils in mouse blood. IL-18 increased the number of mast cells and IL-18R+ mast cells in the lung as well as increased the mast cell numbers and IL-18BP+ mast cells in the bronchoalveolar lavage fluid (BALF) of OVA-sensitized mice. Thus, basophils and mast cells may be involved in asthma pathogenesis via an IL-18-associated mechanism.