IL-33/sST2 axis is associated with metabolic syndrome and social functioning, but not executive function or processing speed, in schizophrenia

Recent studies suggest that immunological markers may play an important role in the pathophysiology of schizophrenia. This study aimed to investigate serum interleukin-33 (IL-33) and soluble suppression of tumorigenicity-2 (sST2) levels and their relationship with metabolic syndrome, social functioning, executive functioning and processing speed in schizophrenia. In this case-control study, patients with schizophrenia ( n = 39), their healthy siblings ( n = 24), and healthy controls ( n = 25) were included. Serum IL-33 and sST2 levels were measured using enzyme-linked immunosorbent assay. Metabolic syndrome parameters were also assessed. Group comparisons and correlation analyses were performed, and receiver operating characteristic analysis was used to determine cut-off values. Patients with schizophrenia had significantly higher IL-33 and lower sST2 levels compared to healthy controls. IL-33 levels were similar between healthy siblings and controls. There was no significant difference in sST2 levels between siblings and the other groups. No significant correlations were found between IL-33, sST2, or their ratio and neurocognitive performance scores. Metabolic parameters were also not associated with neurocognitive measures. These findings suggest that IL-33 and sST2 are associated with schizophrenia-related immune alterations and functional outcomes. However, given the exploratory nature of the study, the small cross-sectional sample, and the lack of longitudinal data, these results do not support their use as diagnostic or prognostic biomarkers. Further prospective studies with larger and well-characterized cohorts are warranted to confirm these associations and to clarify their clinical and biological relevance.