Evaluation of Interleukin-33 and Interleukin-35 Levels and Their Correlation with Clinical and Immunological Parameters in Patients with Hydatid Cyst Disease
ackground: Cystic echinococcosis (CE), which develops following infection with the larval stage of the dog tapeworm Echinococcus granulosus, is a chronic neglected zoonotic disease that represents a major public health concern worldwide. Host-parasite interactions paradigm is based on the cytokines regulation finely modulating immune polarization between survival and clearance. Objectives: The purpose of the study was to assess serum IL-33 and IL-35 levels of in Cystic echinococcosis (CE) patients and to analyze their precise relations to the patient's age, cyst burden (size and number), and (IgE, CRP and ESR) markers. Materials and Methods: A case-control study was performed that included a total of 75 participants (45 CE patients and 30 age- and sex - matched healthy controls). Samples were collected from patients at Al-Sadr Teaching Hospital, Al-Hakeem General Hospital, and Al-Furat Al-Awsat Hospital, in Najaf Governorate, Iraq between September 2025 and February 2026. The age of the participating cohort varied between 18-65 years. Serum IL-33, IL-35, and total IgE levels were measured by specific commercial ELISA kits, whereas C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured by conventional semi-quantitative latex agglutination and Westergren methods, respectively. Performance in diagnosis was determined using the curve analysis of ROC (Receiver Operating Characteristic). Results: Serum IL-33 level, as well as total IgE, CRP and ESR were significantly higher in the CE patients than in the healthy controls. In contrast, circulating IL-35 was markedly and significantly decreased in the patients. Analysis of age groups did not indicate any significant effect on cytokine expressions. On the other hand, higher IL-33 and lower IL-35 levels were significantly related to advanced disease (multiple and large sized cysts). Strong Pearson correlations were found between these interleukins and the inflammatory markers under investigation. ROC curves confirmed high diagnostic accuracy for both cytokines. Conclusion: The increase in levels of IL-33 in the clinical setting Elevated IL-33 and reduced IL-35 levels were associated with cystic echinococcosis and greater disease severity, facilitating a prevailing Th2 bias, while the profound deficiency of IL-35 signifies the collapse of compensatory suppressive mechanisms, enabling parasite persistence and progressive inflammatory severity. Both cytokines showed promising diagnostic performance.