Visceral ischemia-reperfusion injury promotes tumor necrosis factor (TNF) and interleukin-1 (IL-1) dependent organ injury in the mouse.
Acute visceral ischemia and subsequent reperfusion injury, which accompanies the surgical repair of a thoracoabdominal aorta aneurysm, is associated with high rates of morbidity and mortality. The purpose of the present study was to determine whether endogenous tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) production contributes to organ dysfunction in animals subjected to visceral ischemia secondary to 30 min of supraceliac aortic occlusion. C57BL6/j mice were treated with either a TNF binding protein (TNF-bp-10 mg/kg) or an anti-IL-1 receptor type 1 antibody (150 micrograms) 2 h prior to 30 min of supraceliac aortic occlusion. An additional group of mice received 30 min of infrarenal aortic occlusion to determine the contribution of lower torso ischemia-reperfusion injury to the changes seen following supraceliac aortic occlusion. Visceral organ ischemia for 30 min produced by supraceliac aortic occlusion followed by 2 h of reperfusion produced measurable TNF-alpha in 38% of untreated mice, but TNF-alpha was undetectable in both sham-operated mice and following infrarenal aortic occlusion. After 2 h of reperfusion, lung myeloperoxidase levels were significantly elevated in the mice experiencing visceral ischemia-reperfusion compared with either a sham operation or infrarenal ischemia-reperfusion (11.6 +/- 1.3 U/g vs. 3.4 +/- .2 U/g and 3.7 +/- 1.0 U/g, respectively, p < .05). Pretreatment with TNF-bp and anti-IL-1 antibody decreased lung neutrophil recruitment (7.2 +/- 1.2 U/g and 4.6 +/- 1.1 U/g) and capillary membrane permeability changes in mice following visceral ischemia-reperfusion. The present study demonstrates that brief (30 min) clinically relevant visceral ischemia produces TNF-alpha and IL-1 dependent lung injury.
Welborn
M B
MB
Department of Surgery, University of Florida College of Medicine, Gainesville 32610, USA.
Douglas
W G
WG
Abouhamze
Z
Z
Auffenburg
T
T
Abouhamze
A S
AS
Baumhofer
J
J
Seeger
J M
JM
Pruitt
J H
JH
Edwards
P D
PD
Chizzonite
R
R
Martin
D
D
Moldawer
L L
LL
Harward
T R
TR
D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D002199:Capillary Permeability; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000293:injuries / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014656:Vascular Surgical Procedures / Q000379:methods
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D001219:Aspartate Aminotransferases