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Transcript
European Respiratory Society Annual Congress 2013 Abstract Number: 1707 Publication Number: P1888 Abstract Group: 10.1. Respiratory Infections Keyword 1: Exacerbation Keyword 2: Infections Keyword 3: Viruses Title: Impact of IL-13 on RSV infection in vitro and in vivo Dr. Carina 15715 Gross [email protected] 1, Dr. Julie 15716 Coote [email protected] 1, Mrs. Lorna 15717 Edwards [email protected] 1, Mr. Luke 15718 Bevan [email protected] 1, Dr. Michael 15719 Jarman [email protected] 1, Dr. Henry 15722 Danahay [email protected] 1 and Dr. Gerald 15723 Dubois [email protected] 1. 1 Respiratory Diseases, Novartis Institutes for Biomedical Research, Horsham, West Sussex, United Kingdom, RH12 5AB . Body: Virus-induced exacerbations of asthma, COPD and cystic fibrosis (CF) have recently been linked to an impaired innate immune response in epithelial cells. The impaired response to viral infection is characterized by reduced interferon production and increased viral replication. However, the underlying mechanisms as well as the impact of the inflammatory background in these patients are still largely unknown. In this study we investigated the role of IL-13, a key inflammatory cytokine, on innate immune responses in vitro and in vivo. We initially used Poly[I:C], a synthetic TLR3 ligand, to mimic viral infections in well-differentiated human bronchial epithelial cells (HBEC). In normal HBEC Poly[I:C] induced an innate immune response marked by up-regulation of typical genes as well as enhanced chemokine and cytokine release. A similar response was observed in HBEC infected with respiratory syncytial virus (RSV). Pre-treatment of HBECs with IL-13, however, significantly reduced the response to Poly[I:C] as well as to RSV infection as shown by attenuation of IFN-l and IFN- related genes and decreased release of pro-inflammatory cytokines. Interestingly, in IL-13 pre-treated cells we found a reduced viral load and shedding compared to infected control cells. IL-13 pre-treatment of mice prior to RSV infection led to reduced RSV levels in the lung and prevented RSV-induced weight loss.
