INTERLEUKINE-33 AND SOLUBLE ST2 AND THEIR CORRELATION WITH ASTHMA SEVERITY AND AS FUTURE THERAPEUTIC TARGETS.

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 which is a transmembrane form and a soluble ST2 (sST2) which is 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 levels of IL-33 and its receptor sST2 in patients with bronchial asthma to assess if the serum levels of IL-33 and/or sST2 may be markers of the disease severity and potential therapeutic targets.
Patients and methods: This study was carried out at Microbiology & Immunology and Chest Departments, Faculty of Medicine, Zagazig University Hospitals during the period from December 2012 to September 2013.The study included 30 patients diagnosed as bronchial asthma . Patients were classified to two groups: Group I: included 15 patients (8 males and 7 females) with a mean age of 36.2  15.8 during exacerbations of bronchial asthma. Group 2: include 15 patients (8 males and 7 females) with a mean age of 37.3  12.8. They were stable asthmatic patients. There were 30 normal healthy persons as a control group. All patients were subjected to, full medical history, general and local examinations, Plain chest X-ray PA and lateral views, pulmonary function tests, Liver and kidney functions tests, intradermal skin prick test, measurement of serum levels of IL-33 (WKEA MED), soluble ST2 (sST2) (OmniKine) and total IgE (IMMUNOSPEC) by enzyme linked immunosorbent technique using commercial kits.
Results: There was a high significant increase in the mean serum levels of IL-33 in both groups of patients (p < 0.001) with the highest mean serum level 960 ± 336 ng/L in group 1 followed by 732.2 ± 68.3 ng/L in group 2 while the normal control group mean serum level was 174 ± 41 ng/L. As regards serum levels of sST2, there was a high significant increase in its mean levels in both groups of patients (p < 0.001) with the highest mean serum level 96.8 ± 25 pg ∕ ml in group 1 followed by 83.3 ± 5.3 pg∕ml in group 2 while the normal control mean serum level was 33.9 ± 9.6 pg∕ml. In acute exacerbated patients there was significant – ve correlation between FEV1% and serum levels of IL-33 and in stable asthmatic patients there was significant + ve correlation between PEFR variability and serum levels 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 therapeutic targets in bronchial asthma.
Key words: Interleukin-33 , soluble ST2 , bronchial asthma.