Liver cytokine production and ICAM-1 expression following bone fracture, tissue trauma, and hemorrhage in middle-aged mice.
Although studies have indicated that hemorrhagic shock and resuscitation produces hepatic damage by mechanisms involving adhesion molecules in endothelial cells and hepatocytes, it is not known if there is any difference in the extent of hepatic damage following bone fracture, soft tissue trauma, and hemorrhage (Fx-TH) between young and middle-aged animals. To study this, young (6-8 wk) and middle-aged (approximately 12 mo) C3H/HeN male mice were subjected to a right lower leg fracture, soft tissue trauma, (i.e., midline laparotomy), and hemorrhage (blood withdrawal to decrease the blood pressure to 35 +/- 5 mmHg for 90 min) followed by resuscitation with four times the shed blood volume in the form of lactated Ringer solution. Mice were euthanized 24 h later, and liver tissues were harvested. Total bilirubin levels in the hepatocyte extract increased markedly following Fx-TH in both groups of mice; however, the increase in middle-aged mice was significantly higher compared with young mice. TNF-alpha and IL-6 levels in the hepatocyte extract following Fx-TH increased significantly in middle-aged mice but remained unchanged in young mice. IL-10 levels significantly decreased in middle-aged mice following Fx-TH but remained unchanged in young mice. Kupffer cells from middle-aged mice produced significantly higher IL-6 and IL-10 levels compared with young mice. Protein levels and mRNA expression of ICAM-1 in hepatocytes were also significantly higher in middle-aged mice compared with young mice following Fx-TH. These results collectively suggest that the extent of hepatic damage following Fx-TH is dependent on the age of the subject.
Matsutani
Takeshi
T
Center for Surgical Research, University of Alabama, G 094 Volker Hall, 1670 Univ. Blvd., Birmingham, AL 35294-0019, USA.
Kang
Shih-Ching
SC
Miyashita
Masao
M
Sasajima
Koji
K
Choudhry
Mashkoor A
MA
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000375:Aging / Q000502:physiology*; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D050723:Fractures, Bone / Q000150:complications / Q000503:physiopathology*; D006470:Hemorrhage / Q000209:etiology / Q000503:physiopathology*; D022781:Hepatocytes / Q000276:immunology / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000276:immunology / Q000502:physiology; D008099:Liver / Q000276:immunology / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014947:Wounds and Injuries / Q000503:physiopathology*
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D001663:Bilirubin