Differential effect of anti-TNF-α antibody on proinflammatory cytokine release by kupffer cells following liver ischemia and reperfusion

To study the role of tumor necrosis factor-alpha (TNF-alpha) for induction of the proinflammatory cytokine cascade after liver ischemia and reperfusion (I/R), rats were injected intraperitoneally with anti-TNF-alpha monoclonal antibodies (mAb) or placebo (IgG1) 30 min prior to global hepatic ischemi...

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Bibliographic Details
Published in:Shock (Augusta, Ga.) Ga.), 1999-06, Vol.11 (6), p.391-395
Main Authors: WANNER, G. A, MÜLLER, P. E. M, ERTEL, W, BAUER, M, MENGER, M. D, MESSMER, K
Format: Article
Language:English
Subjects:
Animals
Antibodies - immunology
Antibodies - pharmacology
Biological and medical sciences
Cytokines - drug effects
Cytokines - metabolism
Gastroenterology. Liver. Pancreas. Abdomen
Inflammation - metabolism
Interleukin-1 - metabolism
Interleukin-6 - metabolism
Ischemia - metabolism
Kupffer Cells - drug effects
Kupffer Cells - metabolism
Liver - blood supply
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Other diseases. Semiology
Rats
Rats, Sprague-Dawley
Reperfusion
Tumor Necrosis Factor-alpha - immunology
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Summary:To study the role of tumor necrosis factor-alpha (TNF-alpha) for induction of the proinflammatory cytokine cascade after liver ischemia and reperfusion (I/R), rats were injected intraperitoneally with anti-TNF-alpha monoclonal antibodies (mAb) or placebo (IgG1) 30 min prior to global hepatic ischemia. Blood levels of TNF-alpha, interleukin (IL)-1alpha and -6 were determined. In addition, Kupffer cells (KC) were harvested after 60 min of reperfusion and spontaneous cytokine release was measured. Sham-operated animals were used as controls. Levels of proinflammatory cytokines in serum and KC supernatants were detected using specific bioassays and ELISA. Liver I/R resulted in increased (p < .01) serum levels of TNF-alpha, IL-1alpha, and IL-6, which was associated with an enhanced (p < .05) release of these cytokines by KC. In vivo pretreatment with anti-TNF-alpha mAb led to complete neutralization of TNF-alpha serum levels and decreased (p < .01) IL-6 levels (-62%). Moreover, anti-TNF-alpha mAb markedly (p < .05) decreased the release of TNF-alpha (-69%) and IL-6 (-56%) by KC, while IL-1alpha was not affected. These data indicate that TNF-alpha produced early after liver I/R triggers both its own secretion as well as IL-6 release by KC during reperfusion while the release of IL-1alpha occurs independent from TNF-alpha.
ISSN:1073-2322
1540-0514