Role of IL‐18 in atopic asthma is determined by balance of IL‐18/IL‐18BP/IL‐18R

Abstract

It is recognized that IL‐18 is related to development of asthma, but role of IL‐18 in asthma remains controversial and confusing. This is largely due to lack of information on expression of IL‐18 binding protein (BP) and IL‐18 receptor (R) in asthma. In this study, we found that plasma levels of IL‐18 and IL‐18BP were elevated in asthma. The ratio between plasma concentrations of IL‐18 and IL‐18BP was 1:12.8 in asthma patients. We demonstrated that 13‐fold more monocytes, 17.5‐fold more neutrophils and 4.1‐fold more B cells express IL‐18BP than IL‐18 in asthmatic blood, suggesting that there is excessive amount of IL‐18BP to abolish actions of IL‐18 in asthma. We also discovered that more IL‐18R+ monocytes, neutrophils and B cells are located in asthmatic blood. Once injected, IL‐18 eliminated IL‐18R+ monocytes in blood, but up‐regulated expression of IL‐18R in lung macrophages of OVA‐sensitized mice. 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. Therefore, IL‐18R blocking or IL‐18BP activity enhancing therapies may be useful for treatment of asthma.

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

“…A total of 31 patients with asthma and 14 HC subjects were recruited in the study. Their general characteristics and diagnostic criteria were previously described . Informed consent was obtained from each volunteer according to the declaration of Helsinki in agreement with the ethical committee of the General Hospital of Shenyang Military Region of PLA, with the Second Affiliated Hospital of Shenyang Medical College or with the First Affiliated Hospital of Jinzhou Medical University.…”

“…Informed consent was obtained from each volunteer according to the declaration of Helsinki in agreement with the ethical committee of the General Hospital of Shenyang Military Region of PLA, with the Second Affiliated Hospital of Shenyang Medical College or with the First Affiliated Hospital of Jinzhou Medical University. The procedure for collecting and treating peripheral blood specimens was described previously . For certain patients, sputum was collected immediately after admission (during the acute exacerbation stage).…”

“…Mice were sensitized and challenged with an OVA solution following a procedure described previously . Normal saline (1 mL) containing 1 mmol/L EDTA was infused into the unilateral lung for 2 minutes before the animals were sacrificed and their bronchoalveolar lavage fluid (BALF) collected.…”

Altered expression of IL-18, IL-18 binding protein and IL-18 receptor in blood monocytes of patients with allergic rhinitis

“…The procedures for detecting IL-18, IL-18BP and IL-18R expression in human peripheral blood monocytes were mainly adopted from a previous study by Zhang et al [13]. Briefly, whole blood cells were challenged with or without ASWAE, PPAE, or DPAE (all at a concentration of 1.0 μg/mL) for 1 h, and isolated CD14 + monocytes were challenged for 10, 30 and 60 min at 37°C.…”

“…These suggest an imbalance between IL-18 and IL-18BP expression may account for increased IL-18 activity in AR. Indeed, we reported recently that the role of IL-18 in atopic asthma is determined by the balance of IL-18/IL-18BP/IL-18R [13]. Since level of circulating IL-18BP in AR plasma/serum has not been reported, we examined level of IL-18BP in AR plasma in the present study.…”