title: IL-10 deficiency augments acute lung but not liver injury in hemorrhagic shock.
abstract: In hemorrhagic shock and trauma, patients are prone to develop systemic inflammation with remote organ dysfunction, which is thought to be caused by pro-inflammatory mediators. This study investigates the role of the immuno-modulatory cytokine IL-10 in the development of organ dysfunction following hemorrhagic shock. Male C57/BL6 and IL-10 KO mice were subjected to volume controlled hemorrhagic shock for 3h followed by resuscitation. Animals were either sacrificed 3 or 24h after resuscitation. To assess systemic inflammation, serum IL-6, IL-10, KC, and MCP-1 concentrations were measured with the Luminex multiplexing platform; acute lung injury (ALI) was assessed by pulmonary myeloperoxidase (MPO) activity and lung histology and acute liver injury was assessed by hepatic MPO activity, hepatic IL-6 levels, and serum ALT levels. There was a trend towards increased IL-6 and KC serum levels 3h after resuscitation in IL-10 KO as compared to C57/BL6 mice; however this did not reach statistical significance. Serum MCP-1 levels were significantly increased in IL-10 KO mice 3 and 24 h following resuscitation as compared to C57/BL6 mice. In IL-10 KO mice, pulmonary MPO activity was significantly increased 3 h following resuscitation and after 24 h histological signs of acute lung injury were more apparent than in C57/BL6 mice. In contrast, no significant differences in any liver parameters were detected between IL-10 KO and C57/BL6 mice. Our data indicate that an endogenous IL-10 deficiency augments acute lung but not liver injury following hemorrhagic shock.
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh, Kaufmann Medical Building, Suite 1010, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. Kobbe.Philipp@gmx.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Kobbe
authors.forename: Burkhard
authors.initials: B
authors.lastname: Stoffels
authors.forename: Joachim
authors.initials: J
authors.lastname: Schmidt
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Dmitry W
authors.initials: DW
authors.lastname: Gutkin
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bauer
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Pape
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology* / Q000473:pathology; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000293:injuries* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000097:blood / Q000276:immunology
chemical_list: D015850:Interleukin-6; D016753:Interleukin-10; D009195:Peroxidase