Induction of Interleukin-1 Beta (IL-1β) is a Critical Component of Lung Inflammation During Influenza A (H1N1) Virus Infection

Cytokine storm during influenza virus infection is recognized as a predictor of morbidity and mortality. To verify the cellular effects of influenza-induced cytokines in primary normal lung cells, human pulmonary microvascular endothelial cells (HMVECs) and lung fibroblast cells (MRC-5 cells) were infected with influenza virus H1N1. H1N1 infection induced the transcription of various genes encoding cytokines and chemokines such as interleukin-1 beta (IL-1), IL-6, IL-8, IL-12A, tumor necrosis factor alpha (TNF-), and chemokine (C-C motif) ligand 5 (CCL5) in both endothelial cells and lung fibroblasts. Among them, IL-1 induction by influenza infection increased the inflammation of lung cells; conversely, blockade of IL-1 signals with an IL-1 receptor antagonist or a neutralizing antibody alleviated influenza-driven inflammation. In conclusion, these data suggest that secreted IL-1 by the endothelial cells contributes to influenza-induced inflammation, and blockade of IL-1 signals is a potential treatment or therapeutic target for influenza-induced inflammation. J. Med. Virol. 87:1104-1112, 2015. (c) 2015 Wiley Periodicals, Inc.