Clinical Significance of the IL-33/sST2 Axis and Vitamin D Status in the Assessment of Disease Severity and Exacerbation Risk in Asthma: A Prospective Controlled Study.

Background: Asthma is a heterogeneous chronic inflammatory airway disease characterized by recurrent exacerbations and variable airflow limitation. Epithelial-derived alarmins, particularly interleukin-33 (IL-33) and its receptor ST2, play key roles in type 2 inflammation. The soluble form of ST2 (sST2) acts as a decoy receptor regulating IL-33 signaling. Vitamin D is an important immunomodulator influencing airway inflammation, but its interaction with the IL-33/ST2 pathway remains unclear. Objective: To evaluate the association between serum IL-33, sST2, and 25-hydroxyvitamin D [25(OH)D] levels with asthma severity and exacerbation status, and to assess their potential as clinical biomarkers. Methods: This study enrolled 52 adult asthma patients (27 experiencing exacerbation and 25 in remission) and 28 healthy controls. Serum levels of IL-33 and sST2 were measured using enzyme-linked immunosorbent assays, while 25(OH)D concentrations were determined via electrochemiluminescence immunoassay. Results: Serum sST2 levels were significantly higher and 25(OH)D levels significantly lower in asthma patients compared with controls (p < 0.000 for both). Serum IL-33 levels did not differ significantly between groups (p > 0.05). During exacerbation, sST2 levels were markedly elevated compared with remission (p < 0.001), whereas vitamin D levels were significantly reduced (p = 0.038). A significant negative correlation was identified between sST2 and 25(OH)D (r = -0.333, p = 0.016). Conclusions: The presence of asthma and the severity of exacerbations are associated with elevated circulating sST2 levels and reduced vitamin D levels. These findings suggest a regulatory interaction between vitamin D and the IL-33/ST2 axis in airway inflammation and indicate that targeting this axis could be a potential therapeutic strategy.