Tofacitinib suppressed remodeling of pulmonary eosinophilic vasculitis in a murine model

Objective: We examined the effects of tofacitinib on vascular remodeling-including intraluminal myofibroblast proliferation-in a murine model of allergic vasculitis with eosinophil infiltration. Methods:We exposed C57BL/6 mice to ovalbumin (OVA) and aluminum and exposed the positive controls to aerosolized OVA daily for 7 days.We administered tofacitinib (0.1 g/kg) intraperitoneally to the other group of mice in parallel with daily exposure to aerosolized OVA for 7 days.On days 3 and 7, we performed bronchoalveolar lavage (BAL) and excised the lungs for pathological analysis.We determined histological findings of vasculitis and measured concentrations of IL-4, IL-5, IL-6, IL-13, and TGF-β in the BAL fluid (BALF).We then performed a semi-quantitative analysis of pathological changes in the pulmonary arteries according to the severity of vasculitis.Results: In mice treated with tofacitinib, the number of eosinophils in the BALF was reduced significantly when compared with that from control mice treated with just OVA.In the tofacitinib-treated group, TGF-β concentration in the BALF was significantly decreased, pathological scores were significantly reduced, and the number of intraluminal myofibroblasts in the pulmonary arteries was lower than in the control group.Conclusion: Tofacitinib reduced eosinophil infiltration and decreased IL-4, IL-5, IL-6, IL-13, and TGF-β in this murine model of allergic vasculitis with eosinophil infiltration.Our data suggest that tofacitinib suppresses pulmonary vascular remodeling through JAK inhibition.