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Inhibition of the release of soluble tumor necrosis factor receptors in experimental endotoxemia by an anti-tumor necrosis factor-α antibody

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Abstract

The role of tumor necrosis factor-α in the shedding of soluble tumor necrosis factor receptors in endotoxemia was investigated. The appearance of the soluble tumor necrosis factor receptors was assessed in four healthy volunteers following an intravenous injection of tumor necrosis factor-α and in eight chimpanzees after intravenous administration of endotoxin in the absence or presence of concurrent treatment with a neutralizing anti-tumor necrosis factor-α monoclonal antibody. Injection of tumor necrosis factor-α in humans elicited a significant, instantaneous (after 15 min) increase in the plasma concentrations of both types of soluble tumor necrosis factor receptors. In chimpanzees, treatment with the anti-tumor necrosis factor-α antibody completely neutralized endotoxin-induced tumor necrosis factor-α activity. The release of soluble tumor necrosis factor receptors was strongly (80–90%) inhibited in the presence of the neutralizing antibody. Our results indicate that tumor necrosis factor-α is a prime mediator of endotoxin-induced release of its own soluble receptors.

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Authors and Affiliations

  1. Pharmaceutical Research-New Technologies, Hoffmann-La Roche, Basel, Switzerland

    Harald Gallati

  2. Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Room G1-113, Academic Medical Center, Meibergdreef 9, 1105, AZ Amsterdam, The Netherlands

    Jaap Jansen, Tom van der Poll, Marcel Levi, Hugo ten Cate, Jan W. ten Cate & Sander J. H. van Deventer

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  1. Jaap Jansen
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  2. Tom van der Poll
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  3. Marcel Levi
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  4. Hugo ten Cate
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  5. Harald Gallati
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  6. Jan W. ten Cate
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  7. Sander J. H. van Deventer
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Jansen, J., van der Poll, T., Levi, M. et al. Inhibition of the release of soluble tumor necrosis factor receptors in experimental endotoxemia by an anti-tumor necrosis factor-α antibody. J Clin Immunol 15, 45–50 (1995). https://doi.org/10.1007/BF01489489

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