IL-10 deficiency augments acute lung but not liver injury in hemorrhagic shock.
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.
Kobbe
Philipp
P
Department of Orthopaedic Surgery, University of Pittsburgh, Kaufmann Medical Building, Suite 1010, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. Kobbe.Philipp@gmx.de
Stoffels
Burkhard
B
Schmidt
Joachim
J
Tsukamoto
Takeshi
T
Gutkin
Dmitry W
DW
Bauer
Anthony J
AJ
Pape
Hans-Christoph
HC
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
D015850:Interleukin-6; D016753:Interleukin-10; D009195:Peroxidase