Exploring the Potential Role of Interleukin-33 in Inducing Eosinophil-Mediated Fibrosis in Hepatic Alveolar Echinococcosis

BACKGROUND: Alveolar echinococcosis (AE) is a serious zoonotic parasitic disease. This study aimed to investigate the mechanisms underlying the formation of the dense fibrotic band surrounding hepatic alveolar echinococcosis (HAE) lesions, which impedes chemotherapeutic drug penetration. Additionally, the roles of Interleukin-33 (IL-33) and eosinophils in the progression of fibrosis within this band were examined. METHODS: IL-33/suppression of tumorigenicity 2 (ST-2) expression levels were compared between patients with HAE and healthy controls, as well as between close to lesion tissues (CLT) and distant from the lesion tissues (DLT) using enzyme-linked immunosorbent assay (ELISA), western blot, and immunohistochemistry. Immunofluorescence co-localization analysis was performed to examine IL-33/ST-2 and eosinophil distribution. Masson's trichrome staining was used to evaluate fibrosis in AE lesions. Cellular assays were carried out to assess the effects of IL-33 on eosinophil phagocytosis and migration, as well as its impact on α-smooth muscle actin (α-SMA) expression in hepatic stellate cells (HSCs). RESULTS: < 0.05), with IL-33/ST-2 and eosinophils exhibiting a highly consistent distribution within CLT. Masson's trichrome staining confirmed increased fibrosis in CLT. Cellular assays showed that IL-33 enhanced eosinophil phagocytosis and migration, while IL-33 stimulation upregulated α-SMA expression on the HSC surface, with this effect being more pronounced in the presence of eosinophils. CONCLUSION: IL-33 contributed to microenvironmental fibrosis within AE lesions via eosinophil-mediated mechanisms, highlighting a potential therapeutic target to improve chemotherapy efficacy in patients with AE.