Medical College of Wisconsin
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The production of tumor necrosis factor alpha and the development of a pulmonary capillary injury following hepatic ischemia/reperfusion. Transplantation 1990 Feb;49(2):268-72 PMID: 2305455

Pubmed ID



The large mass of fixed macrophages resident in the liver make it a potentially rich source of cytokines. We have previously demonstrated that an isolated and severe ischemia/reperfusion injury to the liver results in cytokine release, specifically tumor necrosis factor alpha, and that TNF is then involved in the development of pulmonary pathology. This study was designed to determine the kinetics of TNF release following varying periods of hepatic ischemia and to further investigate the acute lung injury that follows. Suprahepatic blood samples were obtained at serial time points following a 45-, 60-, 75-, or 90-min ischemic insult to a segment of the rat liver with subsequent reperfusion. Using a bioassay based on the WEHI 164 cell line, plasma TNF levels were measured in all experimental animals; sham-operated control animals had undetectable levels. Changes in pulmonary capillary permeability were then measured using a standard 125I-labeled albumin washout technique following a 90-min ischemic insult with subsequent reperfusion. A significant increase in the mean permeability index was observed 9 to 12 hr following hepatic reperfusion (.601 +/- 102 as compared with .114 +/- .085 in sham-operated controls, P less than 0.005). Animals treated with anti-TNF antiserum prior to the induction of hepatic ischemia had a significantly reduced pulmonary capillary leak compared to animals pretreated with rabbit serum without TNF-blocking properties (.184 +/- .029 versus .694 +/- 052 for the control serum, P less than 0.005). TNF release follows both moderate and severe ischemic injury to the liver and the results reported here implicate TNF as an important mediator of increased pulmonary capillary permeability. These experiments confirm previous histologic studies that demonstrated pulmonary edema and intra-alveolar hemorrhage following hepatic ischemia/reperfusion, with subsequent blockade of the histologic injury by pretreatment with anti-TNF antiserum.

Author List

Colletti LM, Burtch GD, Remick DG, Kunkel SL, Strieter RM, Guice KS, Oldham KT, Campbell DA Jr


Keith T. Oldham MD Professor in the Surgery department at Medical College of Wisconsin


2-s2.0-0025218081   176 Citations

MESH terms used to index this publication - Major topics in bold

Capillary Permeability
Liver Circulation
Lung Diseases
Reperfusion Injury
Time Factors
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad