Serum levels of Interleukin-33 and its soluble receptor ST2 in asthmatic patients

Abstract

Interleukin-33 is a member of IL-1 family of cytokines and binds to two receptors: ST2 (IL-1-R1) and IL-1 receptor accessory protein (IL-1RAP). There are two isoforms of ST2 proteins: ST2L, a transmembrane form, and a soluble ST2 (sST2), a secreted form, that can serve as a decoy receptor of IL-33. The IL-33/ST2 signaling pathway activates airway eosinophils that exacerbate airway inflammation. The aim of this study was to analyze the serum level of IL-33 and its receptor sST2 in patients with bronchial asthma to assess if the serum level of IL-33 and/or sST2 may be a marker of the disease severity and potential therapeutic targets. Patients and methods: This study was carried out at the Microbiology & Immunology and Chest departements, Faculty of Medicine, Zagazig University Hospitals during the period from December 2012 to September 2013. The study included 30 patients diagnosed as bronchial asthma according to GINA 2012. Patients were classified into two groups: Group I: included 15 patients 8 males and 7 females with a mean age 36.2 ± 15.8 during exacerbation of bronchial asthma. Group 2: included 15 patients 8 male and 7 female with mean age 37.3 ± 12.8. They were stable asthmatic patients and the last exacerbation was one month ago. There were 30 normal healthy persons as a control group. All patients were subjected to, full medical history, general and local examination, Plain chest X-ray PA and lateral views, pulmonary function tests, Liver and kidney function tests, intradermal skin test, skin prick test, measurement of serum levels of IL-33 (WEKA MED), IL-33 Receptor (soluble ST2) (OmniKine) and total IgE (IMMUNOSPEC) by enzyme linked immunosorbent technique using commercial kits. Results: There was a highly significant increase in the serum level of IL-33 in both groups of patients (p1 < 0.001) with the highest level 960 ± 336 ng/ml in group 1 followed by 732.2 ± 68.3 ng/ml in group 2 while the normal control group serum level was 174 ± 41 ng/ml. As regards serum level of sST2, there was a highly significant increase in its level in both groups of patients (p1 < 0.001) with the highest level 96.8 ± 25 μg/ml in group 1 followed by 83.3 ± 5.3 μg/ml in group 2 while the normal control group serum level was 33.9 ± 9.6 μg/ml. In acute exacerbated patients there was significant −ve correlation between FEV1 and serum level of both total IgE and IL-33 and in stable asthmatic patients there was high significant +ve correlation between PEFR variability and serum level of sST2. Conclusion: The serum levels of IL-33 and its receptor sST2 were markedly elevated in patients with bronchial asthma and this supports the concept of sST2 and Interleukin-33 as a therapeutic target in asthma.

Keywords

• Interleukin-33
• Soluble ST2
• Bronchial asthma