Relevance of tumour necrosis factor-α and interleukin-1-α in the pathogenesis of hypoxia-related organ failure

H. Gerlach, M. Gerlach, Matthias Clauss

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Tumour necrosis factor-α (TNF) and Interleukin-1-α (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.

Original languageEnglish (US)
Pages (from-to)273-285
Number of pages13
JournalEuropean Journal of Anaesthesiology
Volume10
Issue number4
StatePublished - 1993
Externally publishedYes

Fingerprint

Interleukin-1
Tumor Necrosis Factor-alpha
Cytokines
Cell Hypoxia
Endotoxemia
Tumor Necrosis Factor Receptors
Vascular Endothelium
Microcirculation
Atmosphere
Monocytes
Reactive Oxygen Species
Endothelial Cells
Macrophages
Hypoxia
Oxygen

Keywords

  • Hypoxia
  • Interleukin-1
  • Organ failure
  • Reoxygenation
  • Tumour necrosis factor

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Relevance of tumour necrosis factor-α and interleukin-1-α in the pathogenesis of hypoxia-related organ failure. / Gerlach, H.; Gerlach, M.; Clauss, Matthias.

In: European Journal of Anaesthesiology, Vol. 10, No. 4, 1993, p. 273-285.

Research output: Contribution to journalArticle

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