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Modulation of the endothelial procoagulant response to lipopoly-saccharide and tumour necrosis factor-α in-vitro: The effects of dexamethasone, pentoxifylline, iloprost and a polyclonal anti-human IL-1α antibody

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Abstract

Endothelial expression of tissue factor (TF), a potent procoagulant molecule, is increased in response to inflammatory mediators such as lipopolysaccharide (LPS), tumour necrosis factor (TNF) and interleukin-1 (IL-1). We have examined the effects of three antiinflammatory agents and a polyclonal anti-human IL-1α antibody on the human endothelial TF response toE. coli 0111:B4 LPS and recombinant TNFα (rTNFα) in vitro. In contrast to the expected inhibitory effect, dexamethasone, pentoxyfilline and iloprost failed to block TF expression when administered simultaneously or 30 minutes prior to stimulation with either LPS or rTNFα. Inhibition of procoagulant activity was demonstrated with the anti-IL-1α antibody, suggesting that endothelial derived IL-1α is partially responsible for the TF response to the agonists employed. The failure of the antiinflammatory agents to inhibit endothelial TF expression highlights the possibility that therapeutic agents that modulate the circulating monocyte response to LPS and TNFα may not ameliorate the endothelial dysfunction that is also induced by these inflammatory mediators.

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Authors and Affiliations

  1. Paediatric Infectious Diseases Unit, Department of Paediatrics, St. Mary's Hospital Medical School, London, UK

    R. S. Heyderman, N. J. Klein, O. A. Daramola & M. Levin

  2. Department of Medicine, Medical School, University of Zimbabwe, P.O. Box A178, Avondale, Harare, Zimbabwe

    R. S. Heyderman

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  3. O. A. Daramola
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  4. M. Levin
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Heyderman, R.S., Klein, N.J., Daramola, O.A. et al. Modulation of the endothelial procoagulant response to lipopoly-saccharide and tumour necrosis factor-α in-vitro: The effects of dexamethasone, pentoxifylline, iloprost and a polyclonal anti-human IL-1α antibody. Inflamm Res 44, 275–280 (1995). https://doi.org/10.1007/BF02032568

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  • DOI: https://doi.org/10.1007/BF02032568

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