title: Liver ischemia and reperfusion induces a systemic inflammatory response through Kupffer cell activation.
abstract: To study the role of Kupffer cells (KC) as a cellular source of proinflammatory cytokines in hepatic ischemia/reperfusion, Sprague-Dawley rats were subjected to 20 min global hepatic ischemia. Sham-operated animals served as controls. Blood levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and interleukin 6 (IL-6) were determined after 10, 30, 60, 120, and 240 min of reperfusion and compared with spontaneous cytokine release by KC isolated after 60 min of reperfusion. Hepatic ischemia/reperfusion resulted in an enhanced (p < .01) spontaneous release of TNF-alpha (+482%), IL-1 alpha (+33%), and IL-6 (+175%) by KC. Kinetic analysis of cytokinemia revealed an early increase (p < .01) of TNF-alpha and IL-1 alpha within minutes upon reperfusion, while an elevation of IL-6 serum levels was observed with a delay of 2 h. Early cytokinemia was associated with dysfunction/injury of the liver, lung, and kidney after 4 and 24 h of reperfusion, respectively. These data indicate that hepatic ischemia/reperfusion results in Kupffer cell activation and increased cytokine levels, which may produce systemic inflammation and may be responsible for tissue injury locally and on remote sites.
authors.affiliation: Institute for Surgical Research, Ludwig-Maximillans University-Munich.
authors.forename: G A
authors.initials: GA
authors.lastname: Wanner
authors.forename: W
authors.initials: W
authors.lastname: Ertel
authors.forename: P
authors.initials: P
authors.lastname: Müller
authors.forename: Y
authors.initials: Y
authors.lastname: Höfer
authors.forename: R
authors.initials: R
authors.lastname: Leiderer
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
authors.forename: K
authors.initials: K
authors.lastname: Messmer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004731:Endotoxins / Q000097:blood; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha