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The study investigates the IL-33/ST-2 pathway's role in hepatic fibrosis during alveolar echinococcosis and evaluates combined treatment efficacy with albendazole.

April 5, 2026Open Access

Therapeutic effects of IL-33/ST-2 pathway inhibition combined with albendazole on hepatic fibrosis and immune regulation in alveolar echinococcosis: in vivo and in vitro evidence

Key Points

The study investigates the IL-33/ST-2 pathway's role in hepatic fibrosis during alveolar echinococcosis and evaluates combined treatment efficacy with albendazole.
Examined IL-33 and ST-2 protein levels in a murine model using immunohistochemistry.
Used flow cytometry to analyze IL-33 and ST-2 expression on eosinophils in various tissues.
Conducted phagocytosis and migration assays on eosinophils and hepatic stellate cells.
Performed Masson staining and liver index measurements for assessing fibrosis and liver health.
Measured immune and hepatic function through spleen index evaluation and serum enzyme levels.
Elevated IL-33 and ST-2 levels were found in hepatic tissues of the AE model.
In vitro results showed that IL-33 and ST-2 promoted fibrosis-related traits in hepatic stellate cells.
Combined therapy resulted in better therapeutic outcomes than monotherapy, leading to reduced liver injury.
Improved liver function and restored immune responses were observed with the combined treatment.

Abstract

Abstract Background This study aimed to examine the role of the interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST-2) signaling pathway in hepatic fibrogenesis within the microenvironment of alveolar echinococcosis (AE). The therapeutic efficacy and immunomodulatory effects of concurrent IL-33/ST-2 pathway inhibition and albendazole (ABZ) treatment were also evaluated. Methods Protein expression levels of IL-33 and ST-2 in liver were examined in a murine model of AE using immunohistochemistry. Flow cytometry was used to detect the expression of IL-33 and ST-2 on eosinophils in the blood, liver, and spleen, respectively. Phagocytosis assays, migration assays, and western blot analysis were performed to investigate the effects of IL-33 and ST-2 on eosinophils and hepatic stellate cells, so as to evaluate their roles in hepatic fibrosis and eosinophil activity. Following targeted suppression of the IL-33/ST-2 signaling pathway in combination with ABZ administration, hepatic fibrosis in liver and therapeutic outcomes were assessed through Masson staining, western blot analysis, and liver index measurements. Immune function was assessed via spleen index evaluation and enzyme-linked immunosorbent assay in blood, while hepatic function was assessed by measuring serum alanine aminotransferase and aspartate aminotransferase levels. Results The AE model demonstrated elevated expression of IL-33 and ST-2 in hepatic tissues. In vitro analyses indicated that IL-33 and ST-2 promoted profibrotic phenotypes, including upregulation of α-smooth muscle actin (α-SMA), in hepatic stellate cells, supporting their role in fibrosis development, and modulated eosinophil activity. Inhibition of IL-33/ST-2 expression, followed by ABZ administration, enhanced therapeutic efficacy, improved liver function parameters, and modulated immune responses in AE mice. Combined therapy led to superior outcomes compared with monotherapy, with evidence of reduced hepatic injury and restored immunological homeostasis. Conclusions The IL-33/ST-2 signaling pathway contributes to the pathogenesis of hepatic fibrosis and immunological dysregulation in AE by influencing eosinophil function. Combined intervention targeting this pathway and albendazole administration confers enhanced therapeutic efficacy for AE, encompassing antifibrotic action, liver function recovery, and immune modulation. Graphical Abstract

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