Febuxostat inhibits airway inflammation and lung fibrosis in a mouse model of lipopolysaccharide-induced lung injury

Reduced adenosine triphosphate (ATP) levels due to mitochondrial dysfunction induces lung injury in acute respiratory distress syndrome (ARDS) .Considering that febuxostat improves mitochondrial dysfunction and reduces ATP consumption, its effects were investigated in a mouse model of lipopolysaccharide (LPS) -induced lung injury.Male C57BL/6 mice were intratracheally stimulated with LPS.Febuxostat was administered for 4 or 10 days, and LPS stimulation was performed on Day 3 of febuxostat treatment.At 24 h or 7 days after LPS stimulation, we collected mouse bronchoalveolar lavage fluid (BALF) for determination of cell count and inflammatory cytokine levels and lung tissue for histopathological analysis of fibrosis.BALF total cell and neutrophil counts were significantly lower in the LPSfebuxostat group than in the LPS-only group at 24 h after LPS stimulation and returned to the same levels as those in the control group in both the LPS-only and LPSfebuxostat groups at 7 days after LPS stimulation.In addition, the percentage of collagen deposition areas in the entire lung field was greater in the LPS-only group than in the control group.Notably, febuxostat treatment reduced lung fibrosis in the LPS-stimulated group.Seven days after LPS stimulation, interleukin (IL) -8 production in the BALF was suppressed in the LPSfebuxostat group but not in the LPS-only group.Febuxostat suppressed lung inflammation and prevented lung fibrosis by reducing IL-8 involvement in fibrosis in a mouse model of LPS-induced lung injury.These findings suggested that febuxostat may improve ARDS-associated lung injury.