Role of IL-17 in LPS-induced acute lung injury: an in vivo study

Abstract

To assess the clinical significance of IL-17 in patients with sepsis-induced acute respiratory distress syndrome (ARDS) and to investigate the effects of IL-17 blocking in a mouse model of acute lung injury (ALI). Significantly increased IL-17 level was found in patients with sepsis-related ARDS compared to healthy controls, whereas significantly increased plasma IL-17 level was also observed in non-survivors compared to that in survivors. According to the data from the mouse ALI model, we found significantly increased IL-17 level in lung tissue lysates, mouse bronchoalveolar lavage fluid (mBALF) and plasma at 6, 12 and 24 h after ALI. Histological analyses revealed that reduced sign of pathological changes and lung injury score in the lungs at 48 h after IL-17 blocking antibody administration. Reduced level of proinflammatory tumor necrosis factor α and increased level of anti-inflammatory factor interleukin-10 were found in both mBALF and plasma. Moreover, IL-17 blocking antibody administration attenuated the expression of RORγt and activity of PI3K-Akt pathway. Increased IL-17 was presented in patients with sepsis-induced ARDS and IL-17 may serve as a biomarker to indicate the severity of ARDS. Moreover, IL-17 antibody administration could relieve the ALI symptom by affecting RORγt level and PI3K pathway.