IL-6 ameliorates acute lung injury in influenza virus infection

• Published in: Scientific reports Vol. 7; no. 1; p. 43829
• Main Authors: Yang, Mei-Lin, Wang, Chung-Teng, Yang, Shiu-Ju, Leu, Chia-Hsing, Chen, Shun-Hua, Wu, Chao-Liang, Shiau, Ai-Li
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.03.2017; Nature Publishing Group
• Subjects: 13/21; 14/1; 14/34; 631/250/127/1219; 631/250/255/1578; 64/60; 96/2; Adaptive immunity; Animals; Apoptosis; Body weight; Cell Line; Cell survival; Cells, Cultured; Dogs; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - virology; Extracellular matrix; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - virology; Humanities and Social Sciences; Humans; Immune clearance; Immune response; Infections; Influenza; Influenza A Virus, H1N1 Subtype - growth & development; Influenza A Virus, H1N1 Subtype - physiology; Interleukin 6; Interleukin-6 - deficiency; Interleukin-6 - genetics; Interleukin-6 - metabolism; Lethality; Leukocyte migration; Lung - metabolism; Lung - pathology; Lungs; Macrophages; Macrophages - metabolism; Macrophages - virology; Madin Darby Canine Kidney Cells; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Orthomyxoviridae Infections - genetics; Orthomyxoviridae Infections - metabolism; Orthomyxoviridae Infections - virology; Phagocytes; Phagocytosis; Rodents; Science; Survival; T cell receptors; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep43829

Interleukin 6 (IL-6) is involved in innate and adaptive immune responses to defend against pathogens. It also participates in the process of influenza infection by affecting viral clearance and immune cell responses. However, whether IL-6 impacts lung repair in influenza pathogenesis remains unclear. Here, we studied the role of IL-6 in acute influenza infection in mice. IL-6-deficient mice infected with influenza virus exhibited higher lethality, lost more body weight and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lung than their wild-type counterparts. Deficiency in IL-6 enhanced proliferation, migration and survival of lung fibroblasts, as well as increased virus-induced apoptosis of lung epithelial cells. IL-6-deficient lung fibroblasts produced elevated levels of TGF-β, which may contribute to their survival. Furthermore, macrophage recruitment to the lung and phagocytic activities of macrophages during influenza infection were reduced in IL-6-deficient mice. Collectively, our results indicate that IL-6 is crucial for lung repair after influenza-induced lung injury through reducing fibroblast accumulation, promoting epithelial cell survival, increasing macrophage recruitment to the lung and enhancing phagocytosis of viruses by macrophages. This study suggests that IL-6 may be exploited for lung repair during influenza infection.