PT - JOURNAL ARTICLE AU - Pratikshya Pandey AU - Andrew Flies AU - Bruce Lyons AU - Gunasegaran Karupiah TI - Tumour necrosis factor and signal transducer and activator of transcription 3 pathways; novel targets to treat severe influenza virus infection AID - 10.1183/13993003.congress-2019.PA2392 DP - 2019 Sep 28 TA - European Respiratory Journal PG - PA2392 VI - 54 IP - suppl 63 4099 - http://erj.ersjournals.com/content/54/suppl_63/PA2392.short 4100 - http://erj.ersjournals.com/content/54/suppl_63/PA2392.full SO - Eur Respir J2019 Sep 28; 54 AB - Excessive early cytokine response i.e. hypercytokinemia and immune cell recruitment are associated with severe influenza virus infection resulting in significant morbidity and mortality. Anti-viral therapies that target virus replication are available, however, are effective only when treatment is started within 2 days of onset of disease symptoms. This highlights the necessity for developing novel methods to combat morbidity and mortality associated with influenza virus infection. Here, we show that immunomodulatory agents such as tumour necrosis factor (TNF) blockade and signal transducer and activator of transcription 3 (STAT-3) inhibitor in combination with an antiviral (oseltamivir) significantly limit the lung pathology. This combination treatment reduces infiltration of inflammatory leukocytes and alveolar oedema in influenza virus infected C57BL/6 mice even when the treatment is started 48 hours post onset of symptoms. Mechanistically, the combination therapy of TNF-blockade or STAT-3 inhibitor with an antiviral significantly downregulate the expression of TNFα, interleukin 6 (IL-6), IL-1α, and C-C motif chemokine ligand 5 (CCL5), which are markedly induced during early response to influenza virus infection and are associated with significant morbidity and mortality. Therefore, targeting TNF or STAT-3 pathway in addition to antivirals could be potential therapeutic approach to treat severe viral infections including, influenza where the host’s inflammatory response is a major component of disease pathogenesis.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA2392.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).