Biochemical, radiological and histological effects of ixekizumab on skin tissue in a bleomycin-induced systemic sclerosis mouse model.

OBJECTIVES: Abnormal T-cell activation, Th17 cells, and IL-17 play a role in inflammation and fibrosis in systemic sclerosis (SSc). Targeting Th17 cells has shown promising therapeutic potential in SSc treatment. This study aimed to investigate the biochemical, radiological, and histological effects of ixekizumab (IXE), an IL-17 blocker, in a bleomycin (BLM)-induced SSc mouse model. METHODS: An experimental study was conducted on 40 female BALB/c mice, randomly divided into four groups: control, BLM, BLM+IXE, and BLM+MMF. SSc was induced by subcutaneous bleomycin administration (1 mg/kg every other day for 21 days). Following fibrosis induction, the BLM+IXE group received a single subcutaneous dose of ixekizumab (1.6 mg/kg), while the BLM+MMF group received oral mycophenolate mofetil (20 mg/kg/day) for 14 consecutive days. Skin tissue samples underwent routine histopathological processing and were stained and evaluated for various parameters using semi-quantitative scoring. Blood levels of TNF-α, TGF-β1, and IL-17A were evaluated, and skin thickness was measured via ultrasound (US). Student's t-test, Fisher's exact test, and ANOVA were used for analysis. A p-value <0.05 was considered statistically significant. RESULTS: TNF-α, TGF-β1, and IL-17A levels were significantly higher in the BLM group than in the control group, whereas IXE and MMF treatment partially reduced these cytokine levels. Histological analysis revealed decreased dermal fibrosis and inflammatory cell infiltration in the BLM+MMF and BLM+IXE groups compared to the BLM group. Skin thickness was greater in the BLM group on US measurements and significantly lower in the treatment groups. CONCLUSIONS: IXE, an IL-17A inhibitor, reduced tissue fibrosis-related changes in a BLM-induced SSc model. This biological agent is thought to suppress mechanisms involved in SSc pathogenesis and showed similar antifibrotic trends to MMF, with no statistically significant differences observed between the two treatment groups for histopathological scores.