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Therapeutic targeting of inflammation and virus simultaneously ameliorates influenza pneumonia and protects from morbidity and mortality
Citation
Pandey, P and Al Rumaih, Z and Tuazon Kels, MJ and Ng, E and KC, R and Malley, R and Chaudhri, G and Karupiah, G, Therapeutic targeting of inflammation and virus simultaneously ameliorates influenza pneumonia and protects from morbidity and mortality, Viruses, 15 pp. 1-18. ISSN 1999-4915 (2023) [Refereed Article]
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Abstract
Influenza pneumonia is a severe complication caused by inflammation of the lungs following infection with seasonal and pandemic strains of influenza A virus (IAV), that can result in lung pathology, respiratory failure, and death. There is currently no treatment for severe disease and pneumonia caused by IAV. Antivirals are available but are only effective if treatment is initiated within 48 h of onset of symptoms. Influenza complications and mortality are often associated with high viral load and an excessive lung inflammatory cytokine response. Therefore, we simultaneously targeted the virus and inflammation. We used the antiviral oseltamivir and the anti-inflammatory drug etanercept to dampen TNF signaling after the onset of clinical signs to treat pneumonia in a mouse model of respiratory IAV infection. The combined treatment down-regulated the inflammatory cytokines TNF, IL-1β, IL-6, and IL-12p40, and the chemokines CCL2, CCL5, and CXCL10. Consequently, combined treatment with oseltamivir and a signal transducer and activator of transcription 3 (STAT3) inhibitor effectively reduced clinical disease and lung pathology. Combined treatment using etanercept or STAT3 inhibitor and oseltamivir dampened an overlapping set of cytokines. Thus, combined therapy targeting a specific cytokine or cytokine signaling pathway and an antiviral drug provide an effective treatment strategy for ameliorating IAV pneumonia. This approach might apply to treating pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | TNF/NF-κB and STAT3 signaling pathways; combined oseltamivir and anti-inflammatory drug treatment; influenza; viral pneumonia |
| Research Division: | Biological Sciences |
| Research Group: | Microbiology |
| Research Field: | Virology |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Treatment of human diseases and conditions |
| UTAS Author: | Pandey, P (Mrs Pratikshya Pandey) |
| UTAS Author: | KC, R (Dr Rajendra KC) |
| UTAS Author: | Malley, R (Dr Roslyn Malley) |
| UTAS Author: | Karupiah, G (Associate Professor Guna Karupiah) |
| ID Code: | 155727 |
| Year Published: | 2023 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2023-03-09 |
| Last Modified: | 2023-03-09 |
| Downloads: | 0 |
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