Longitudinal Changes in Serum Interleukin-33 Levels During Acute Psychotic Relapse and Clinical Improvement in Schizophrenia: An Admission-Discharge Study

Background/Objectives: Schizophrenia pathophysiology has been linked to immune dysregulation, but the role of interleukin-33 (IL-33) during acute psychotic relapse remains insufficiently investigated. This exploratory admission–discharge study aimed to evaluate serum IL-33 levels in inpatients with paranoid schizophrenia and in healthy controls. Methods: Serum IL-33 was measured at midday (12:00 h) and midnight (24:00 h) in 21 inpatients with paranoid schizophrenia and 21 age- and sex-matched healthy controls (HC). Patients were sampled at admission and discharge. HC underwent one sampling day, with blood collected at both 12:00 h and 24:00 h, during the interval between the patients' admission and discharge assessments. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results: PANSS positive and general psychopathology scores decreased from admission to discharge (p < 0.001 and p = 0.008, respectively). Serum IL-33 concentrations were descriptively higher in patients than in HC, but between-group differences were not statistically significant. Midnight serum IL-33 increased from admission to discharge (214.9 ± 358.0 vs. 241.2 ± 379.4 pg/mL; p = 0.028), whereas the midday change was nonsignificant. Age was inversely correlated with IL-33 in patients; associations with antipsychotic dosage and sex were not statistically significant. Conclusions: The midnight increase in IL-33 accompanied clinical improvement, but medication, hospitalization, age, and smoking remain potential confounders. These exploratory findings warrant replication and do not establish IL-33 as a diagnostic or state biomarker.