{"corpus_id":1484010,"paper_sha":"038648e15c198796180e28080f063fa5507eca49","doi":"10.1182/BLOOD.V90.8.3204","arxiv_id":null,"pmid":9376604,"pmcid":null,"mag_id":1795844187,"dblp_id":null,"acl_id":null,"title":"Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines.","year":1997,"publication_date":"1997-10-15","venue":"Blood","journal":{"name":"Blood","pages":"\n          3204-13\n        ","volume":"90 8"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't","Research Support, U.S. Gov't, P.H.S."],"s2_fields_of_study":["Medicine","Environmental Science"],"reference_count":56,"citation_count":872,"influential_citation_count":31,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Bone Marrow Transplantation","mj":true,"ui":"D016026"},{"d":"Cytokines","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D016207"},{"d":"Digestive System","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"},{"q":"radiation effects","mj":false,"ui":"Q000528"}],"ui":"D004064"},{"d":"Dose-Response Relationship, Radiation","mj":false,"ui":"D004307"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Graft vs Host Disease","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"}],"ui":"D006086"},{"d":"Lipopolysaccharides","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D008070"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Inbred C57BL","mj":false,"ui":"D008810"},{"d":"Neoplasms, Experimental","mj":false,"qs":[{"q":"radiotherapy","mj":true,"ui":"Q000532"}],"ui":"D009374"},{"d":"Transplantation Conditioning","mj":false,"qs":[{"q":"adverse effects","mj":true,"ui":"Q000009"}],"ui":"D019172"},{"d":"Tumor Necrosis Factor-alpha","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D014409"},{"d":"Whole-Body Irradiation","mj":true,"ui":"D014916"}],"chemicals":[{"n":"Cytokines","ui":"D016207","reg":"0"},{"n":"Lipopolysaccharides","ui":"D008070","reg":"0"},{"n":"Tumor Necrosis Factor-alpha","ui":"D014409","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://ashpublications.org/blood/article-pdf/90/8/3204/1041385/3204.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/038648e15c198796180e28080f063fa5507eca49","s2_open_access_license":null,"s2_open_access_status":"BRONZE","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"The influence of bone marrow transplantation (BMT) conditioning regimens on the incidence and severity of graft-versus-host disease (GVHD) has been suggested in clinical BMT. Using murine BMT models, we show here an increase in GVHD severity in several donor-recipient strain combinations after intensification of the conditioning regimen by increasing the total body irradiation (TBI) dose from 900 cGy to 1,300 cGy. Increased GVHD was mediated by systemic increases in tumor necrosis factor alpha (TNF alpha). Histologic analysis of gastrointestinal tracts showed synergistic damage by increased TBI and allogeneic donor cells that permitted increased translocation of lipopolysacharide (LPS) into the systemic circulation. In vitro, LPS triggered excess TNF alpha from macrophages primed by the GVH reaction. In addition, macrophages isolated within 4 hours of conditioning were primed in proportion to the TBI dose itself to secrete TNF alpha. Thus, the higher TBI dose increased macrophage priming and increased gut damage after allogeneic BMT, causing higher systemic levels of inflammatory cytokines and subsequent severe GVHD. These data highlight the importance of conditioning in GVHD pathophysiology and suggest that interventions to prevent LPS stimulation of primed macrophages may limit the severity of GVHD after intensive conditioning for allogeneic BMT.","claims":[{"public_id":"cl_904a5a76031324e3cf61fbbb515a0df9","status":"active","text":"Higher total body irradiation and allogeneic donor cells cause synergistic damage to gastrointestinal tracts, permitting increased translocation of lipopolysaccharide into systemic circulation.","confidence":0.9,"contributors":[{"id":32,"public_id":"7c402c1b98","public_label":"뀨 (7c402c1b98)","roles":["extraction"],"url":"https://sah.borca.ai/u/7c402c1b98"},{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["review"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_904a5a76031324e3cf61fbbb515a0df9"},{"public_id":"cl_a370f32a096fe91d804791060525ac00","status":"active","text":"Increased graft-versus-host 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