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Seasonal and pandemic influenza viruses, variola virus (agent of smallpox) and severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102; agent of COVID\u201019) are some leading examples. Viral pneumonia is triggered by excessive inflammation associated with dysregulated cytokine production, termed \u2018cytokine storm\u2019. Several cytokines have been implicated but tumour necrosis factor (TNF) plays a critical role in driving lung inflammation, severe lung pathology and death. Despite this, the exact role TNF plays in the aetiology and pathogenesis of virus infection\u2010induced respiratory complications is not well understood. In this review, we discuss the pathological and immunomodulatory roles of TNF in contributing to immunopathology and resolution of lung inflammation, respectively, in mouse models of influenza\u2010 and smallpox (mousepox)\u2010induced pneumonia. We review studies that have investigated dampening of inflammation on the outcome of severe influenza and orthopoxvirus infections. Most studies on the influenza model have evaluated the efficacy of treatment with anti\u2010inflammatory drugs, including anti\u2010TNF agents, in animal models on the day of viral infection. We question the merits of those studies as they are not transferable to the clinic given that individuals generally present at a hospital only after the onset of disease symptoms and not on the day of infection. We propose that research should be directed at determining whether dampening lung inflammation after the onset of disease symptoms will reduce morbidity and mortality. Such a treatment strategy will be more relevant clinically.<\/jats:p>","DOI":"10.1111\/febs.15782","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T07:54:50Z","timestamp":1614153290000},"page":"883-900","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Targeting tumour necrosis factor to ameliorate viral pneumonia"],"prefix":"10.1111","volume":"289","author":[{"given":"Pratikshya","family":"Pandey","sequence":"first","affiliation":[{"name":"Viral Immunology and Immunopathology Group Tasmanian School of Medicine University of Tasmania Hobart TAS Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6306-4405","authenticated-orcid":false,"given":"Gunasegaran","family":"Karupiah","sequence":"additional","affiliation":[{"name":"Viral Immunology and Immunopathology Group Tasmanian School of Medicine University of Tasmania Hobart TAS Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"e_1_2_21_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30310-4"},{"key":"e_1_2_21_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.10.006"},{"key":"e_1_2_21_4_1","volume-title":"Causes of Pneumonia in Pneumonia","author":"CDC","year":"2020"},{"key":"e_1_2_21_5_1","volume-title":"Viral Pneumonia","author":"Freeman AM","year":"2020"},{"key":"e_1_2_21_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/600383"},{"key":"e_1_2_21_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12065"},{"key":"e_1_2_21_8_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1607.091248"},{"key":"e_1_2_21_9_1","first-page":"41","article-title":"Prevention and control of influenza in persons with chronic obstructive pulmonary disease","volume":"2","author":"Plans\u2010Rubi\u00f3 P","year":"2007","journal-title":"Int J Chronic Obstruct Pulmon Dis"},{"key":"e_1_2_21_10_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-130-5-199903020-00003"},{"key":"e_1_2_21_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002588"},{"key":"e_1_2_21_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3166"},{"key":"e_1_2_21_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/v3060920"},{"key":"e_1_2_21_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020546615229"},{"key":"e_1_2_21_15_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1957.0048"},{"key":"e_1_2_21_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.12.5893"},{"key":"e_1_2_21_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-016-0558-0"},{"key":"e_1_2_21_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206965"},{"key":"e_1_2_21_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1397"},{"key":"e_1_2_21_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2287"},{"key":"e_1_2_21_21_1","first-page":"1","article-title":"Tumor necrosis factors. 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