{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:15:23Z","timestamp":1789820123801,"version":"4.0.1"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health, National Cancer Institute","award":["3U54CA193489-05S5"],"award-info":[{"award-number":["3U54CA193489-05S5"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Introduction<\/jats:title><jats:p>Volatile and intravenous anesthetics may worsen oncologic outcomes in basic science animal models. These effects may be related to suppressed innate and adaptive immunity, decreased immunosurveillance, and disrupted cellular signaling. We hypothesized that anesthetics would promote lung tumor growth via altered immune function in a murine model and tested this using an immunological control group of immunodeficient mice.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>Lewis lung carcinoma cells were injected via tail vein into C57BL\/6 immunocompetent and NSG immunodeficient mice during exposure to isoflurane and ketamine versus controls without anesthesia. Mice were imaged on days 0, 3, 10, and 14 post-tumor cell injection. On day 14, mice were euthanized and organs fixed for metastasis quantification and immunohistochemistry staining. We compared growth of tumors measured from bioluminescent imaging and tumor metastasis in<jats:italic>ex vivo<\/jats:italic>bioluminescent imaging of lung and liver.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>Metastases were significantly greater for immunocompromised NSG mice than immunocompetent C57BL\/6 mice over the 14-day experiment (partial \u03b7<jats:sup>2<\/jats:sup>= 0.67, 95% CI = 0.54, 0.76). Among immunocompetent mice, metastases were greatest for mice receiving ketamine, intermediate for those receiving isoflurane, and least for control mice (partial \u03b7<jats:sup>2<\/jats:sup>= 0.88, 95% CI = 0.82, 0.91). In immunocompetent mice, significantly decreased T lymphocyte (partial \u03b7<jats:sup>2<\/jats:sup>= 0.83, 95% CI = 0.29, 0.93) and monocyte (partial \u03b7<jats:sup>2<\/jats:sup>= 0.90, 95% CI = 0.52, 0.96) infiltration was observed in anesthetic-treated mice versus controls.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>The immune system appears central to the pro-metastatic effects of isoflurane and ketamine in a murine model, with decreased T lymphocytes and monocytes likely playing a role.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0292492","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T17:45:16Z","timestamp":1696959916000},"page":"e0292492","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Immunomodulatory and pro-oncologic effects of ketamine and isoflurane anesthetics in a murine model"],"prefix":"10.1371","volume":"18","author":[{"given":"Dominique","family":"Abrahams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arig","family":"Ibrahim-Hashim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Ackerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7511-2603","authenticated-orcid":true,"given":"Christopher J.","family":"Whelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan B.","family":"Garfinkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Gatenby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6401-5370","authenticated-orcid":true,"given":"Aaron R.","family":"Muncey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"issue":"2","key":"pone.0292492.ref001","doi-asserted-by":"crossref","first-page":"e89693","DOI":"10.1371\/journal.pone.0089693","article-title":"The role of surgery in global health: analysis of United States inpatient procedure frequency by condition using the Global Burden of Disease 2010 framework","volume":"9","author":"J Rose","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pone.0292492.ref002","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12967-018-1389-7","article-title":"Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence","volume":"16","author":"R. 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