SAT0243 EFFECTS OF TOFACITINIB SUPPRESSED PULMONARY VASCULAR REMODELING OF ALLERGIC VASCULITIS IN A MURINE MODEL

Background: We reported allergic granulomatous vasculitis with eosinophil infiltration in an asthma model of C57BL/6 sensitized with ovalbumin (OVA). TGF-btea and IL-6 are thought to play an important role in fibroblasts proliferation and is critical to vascular remodeling in vasculitis. Tofacitinib inhibits vascular endothelial cells proliferation and canalization. Objectives: To elucidate the role of tofacitinib in vascular remodeling of allergic granulomatous vasculitis, we examined the effects of tofacitinib on the vasculitis of the murine model. Methods: C57BL/6 mice (6-8 weeks) were sensitized with ovalbumin (OVA) and alum. The positive controls (n=9) were exposed to aerosolized OVA daily for 7 days. The other group of mice (tofacitinib treated mice(n=9)) were administered with tofacitinib (100mg/kg intraperitoneal administration) in parallel with daily exposure to aerosolized OVA for 7 days. On 7th day, bronchoalveolar lavage (BALF) was performed and the lungs were excised for pathological analysis. Cytokines in BALF were measured. Results: The total cell number and the number of. Eosinophils in BALF on the 7th day were decreased significantly in the tofacitinib-treated mice compared with those of the control-positive mice. The blood eosinophil counts in the positive control increased after OVA inhalation. The blood eosinophil counts in the tofacitinib treated mice were lower on the than those in the positive control. The concentrations of IL-4, IL-5, IL-6 and TGF-beta in BAL fluids reduced significantly in the tofacitinib treated group. The pathological scores reduced significantly in the tofacitinib treated group compared to the positive control group. Intra luminal infiltration and proliferation of Ki67 positive myofibroblasts, IL-6 positive cell and α-SMA positive cells in pulmonary arteries were reduced dramatically in the tofacitinib treated group compared to the positive control group. Conclusion: Tofacitinib suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration. Tofacitinib is a hopeful therapeutic drug for Eosinophilic granulomatosis with polyangiitis. Disclosure of Interests: None declared