{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:40:01Z","timestamp":1761864001320,"version":"3.40.5"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T00:00:00Z","timestamp":1564704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"University of Missouri College of Veterinary Medicine and University of Florida College of Veterinary Medicine"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Medicine &amp; Sci"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Current advances in immunotherapy are an exciting area of study in canine osteosarcoma (<jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content>). The objective of this study was to determine the immune response in dogs with osteosarcoma by measuring stimulated leukocyte production of tumor necrosis factor (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>), interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20106, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 ratios.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole blood was collected from dogs with osteosarcoma receiving non\u2010steroidal anti\u2010inflammatory drugs (<jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content>s, <jats:italic>n<\/jats:italic>\u00a0=\u00a011), dogs with osteosarcoma not receiving <jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content>s (<jats:italic>n<\/jats:italic>\u00a0=\u00a014) and healthy dogs (<jats:italic>n<\/jats:italic>\u00a0=\u00a05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No difference in <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> production was found among healthy and <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> dogs regardless of <jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content> administration following stimulation with lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.410), lipoteichoic acid (<jats:styled-content style=\"fixed-case\">LTA<\/jats:styled-content>) (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.693) or <jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.120). Leukocyte <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 production was greater in all dogs with <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> after stimulation with <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.015), <jats:styled-content style=\"fixed-case\">LTA<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.014) and <jats:styled-content style=\"fixed-case\">PBS<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.034) with no difference between <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> dogs receiving <jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content>s and those not. No differences in <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 were found among healthy controls and dogs with <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> regardless of <jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content> use. There was no difference among groups for <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010stimulated <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 ratios (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.407). For <jats:styled-content style=\"fixed-case\">LTA<\/jats:styled-content>\u2010stimulated leukocytes, the <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 ratio was lower in dogs with <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> than in healthy dogs (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.031) with no difference between <jats:styled-content style=\"fixed-case\">OSA NSAID<\/jats:styled-content> dogs compared to <jats:styled-content style=\"fixed-case\">OSA<\/jats:styled-content> non\u2010<jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content> dogs (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.059). No differences were found in <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.310)\u2010 or <jats:styled-content style=\"fixed-case\">LTA<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.265)\u2010stimulated leukocyte <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 production ratios among groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dogs with osteosarcoma have an altered pro\u2010 and anti\u2010inflammatory immunologic profile compared to healthy dogs regardless of <jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content> use. Further study is indicated to determine the potential prognostic and therapeutic implications of these findings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/vms3.191","type":"journal-article","created":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T16:09:32Z","timestamp":1564762172000},"page":"485-493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dogs with osteosarcoma have altered pro\u2010 and anti\u2010inflammatory cytokine profiles"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-5959","authenticated-orcid":false,"given":"Sandra M.","family":"Axiak\u2010Bechtel","sequence":"first","affiliation":[{"name":"Comparative Oncology Laboratory Department of Veterinary Medicine and Surgery College of Veterinary Medicine University of Missouri Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leanne 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