Relevance of tumour necrosis factor-alpha and interleukin-1-alpha in the pathogenesis of hypoxia-related organ failure.
Tumour necrosis factor-alpha (TNF) and Interleukin-1-alpha (IL-1) are both cytokines which are known to be released by stimulated macrophages during septic events. Because of their influence on the function of the vascular endothelium, TNF and IL-1 contribute to the pathogenesis of hypoperfusion and organ dysfunction. The finding of elevated cytokine levels in patients with hypoxic organ failure, suggesting a relation between systemic oxygen supply and humoral mechanisms, led us to perform laboratory investigations on the relevance of TNF and IL-1 for the pathogenesis of hypoxia-related deterioration of the microcirculation. In vivo studies with anaesthetized rats demonstrated a synergism between hypoxaemia and endotoxaemia on the development of lethal organ failure. In vitro studies with human monocytes showed that a hypoxic atmosphere was not able to induce synthesis or release of TNF and IL-1, whereas re-oxygenation after hypoxia initiated a significant increase in TNF and IL-1 synthesis, probably mediated by oxygen radicals. Finally, experiments with human endothelial cells established that hypoxia is able to induce high affinity receptors for TNF in a time- and dose-dependent manner. These studies demonstrate that hypoxia influences humoral mechanisms which are known to contribute to the pathogenesis of vessel dysfunction, probably through a cytokine-dependent pathway of hypoxia-related organ dysfunction.
Gerlach
H
H
Department of Hematology and Oncology, University Clinic Rudolf Virchow, Free University of Berlin, Germany.
Gerlach
M
M
Clauss
M
M
D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000209:etiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology*; D009102:Multiple Organ Failure / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha