IL-22 significantly reduced hepatic granuloma index and modulated STAT3/β-catenin/let-7a in S. mansoni-infected mice.

The parasitic infection Schistosomiasis mansoni leads to severe hepatic granuloma formation, driven by dysregulated cytokine networks and pro-fibrotic pathways, notably STAT3, Wnt/β-catenin, and microRNA let-7a. Current anthelmintic treatments like praziquantel (PZQ) effectively kill adult worms but often fall short in resolving established granulomas and associated fibrosis. Interleukin-22 (IL-22), an epithelial-targeted cytokine signaling through STAT3, has shown promise in tissue protection and fibrosis modulation, making it a candidate for addressing the inflammatory and fibrotic components of schistosomal liver disease.

Male mice infected with S. mansoni were divided into treatment groups: recombinant IL-22 (0.36 µg/kg intraperitoneally daily × 14 days), a single oral dose of praziquantel (PZQ, 600 mg/kg orally), or a combination of both. Serum levels of TNF-α, IL-17, IL-22, and IgE were quantified using ELISA. Hepatic STAT3 and β-catenin mRNA expression, along with let-7a miRNA expression, were analyzed by quantitative RT-PCR, normalized to GAPDH and U6 snRNA respectively. Granuloma index and developmental phase distribution were assessed histologically.

IL-22 treatment significantly reduced the granuloma index by 11.1% (P < 0.05) and systemic TNF-α by 16.8%, alongside a substantial 69.8% reduction in IgE. This was accompanied by robust upregulation of hepatic STAT3 mRNA by 10.4-fold (P < 0.05) and let-7a miRNA by 10.6-fold (P < 0.05). Concurrently, β-catenin transcripts were downregulated by 48.9% from infected levels (P < 0.05). In contrast, PZQ decreased inflammatory mediators and IgE but did not significantly reduce the granuloma index and paradoxically increased β-catenin expression by 60% from infected levels (P < 0.05).