{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:55:03Z","timestamp":1791248103647,"version":"4.1.0"},"reference-count":65,"publisher":"Radiation Research Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2024,7,25]]},"abstract":"<jats:p>Inflammation is a key factor in both influenza and radiation-induced lung pathophysiology. This implies a commonality of response to pulmonary damage from these insults and suggests exacerbated pathology may occur after combined exposure. We therefore tested the hypothesis that past inflammation from viral infection alters the lung microenvironment and lowers tolerance for radiation injury. Mice were inoculated with influenza A virus (IAV) and three weeks later, after virus clearance, mice received total-body irradiation (TBI). Survival as well as systemic and local lung inflammation were assessed, and strategies to mitigate pulmonary injury were investigated. After IAV infection alone, body condition recovered within 3 weeks, however inflammatory pathways remained active for 15 weeks. IAV infection exacerbated subsequent TBI responses, evident by increased lethality, enhanced histologically evident lung injury and an altered lung macrophage phenotype. To mitigate this enhanced sensitivity, captopril [an angiotensin converting enzyme inhibitor (ACEi)] was administered to limit tissue inflammation, or inflammatory monocyte-derived macrophage recruitment was blocked with a C-C chemokine receptor type 2 (CCR2) inhibitor. Both treatments abrogated the changes in circulating immune cells observed 4 weeks after TBI, and attenuated pro-inflammatory phenotypes in lung alveolar macrophages, appearing to shift immune cell dynamics towards recovery. Histologically apparent lung injury was not improved by either treatment. We show that latent lung injury from viral infection exacerbates radiation morbidity and mortality. Although strategies that attenuate proinflammatory immune cell phenotypes can normalize macrophage dynamics, this does not fully mitigate lung injury. Recognizing that past viral infections can enhance lung radiosensitivity is of critical importance for patients receiving TBI, as it could increase the incidence of adverse outcomes.<\/jats:p>","DOI":"10.1667\/rade-24-00103.1","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T20:01:48Z","timestamp":1721851308000},"page":"552-564","source":"Crossref","is-referenced-by-count":4,"title":["Mitigating Viral Impact on the Radiation Response of the Lung"],"prefix":"10.1667","volume":"202","author":[{"given":"Angela M.","family":"Groves","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole D.","family":"Paris","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl J.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hernady","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, University of Rochester, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Marples","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"38","doi-asserted-by":"crossref","unstructured":"CM Manning, CJ Johnston, CK Reed, et al.  \"Int J Radiat Oncol Biol Phys.\"  86, \"Lung irradiation increases mortality after influenza A virus challenge occurring late after exposure.\" 128 (2013)","DOI":"10.1016\/j.ijrobp.2012.10.019"},{"key":"26","doi-asserted-by":"crossref","unstructured":"Y He, D Thummuri, G Zheng, et al.  \"Transl Res.\"  209, \"Cellular senescence and radiation-induced pulmonary fibrosis.\" 14 (2019)","DOI":"10.1016\/j.trsl.2019.03.006"},{"key":"37","doi-asserted-by":"crossref","unstructured":"CM Manning, CJ Johnston, E Hernady, et al.  \"Radiat Res.\"  179, \"Exacerbation Of Lung Radiation Injury By Viral Infection: The Role Of Clara Cells And Clara Cell Secretory Protein.\" 617 (2013)","DOI":"10.1667\/RR3279.1"},{"key":"23","doi-asserted-by":"crossref","unstructured":"SM. 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