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Blockade of cytokine activity by soluble cytokine receptors

  • Chapter
Novel Cytokine Inhibitors

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

A great number and variety of specific cytokine receptors have been characterised. One feature they have in common is that their extracellular domains (ectodomains) are universally required for cytokine binding. While in general receptors, following cytokine binding, are internalised, many shed their ectodomains, largely in their entirety, from the cell membrane due to enzymatic cleavage (Tab. 1). These intact ectodomains are known as soluble cytokine receptors (sCRs) [1]. More rarely, sCRs are generated by alternative splicing of mRNAs (Tab. 1), where such modification leads to receptors lacking transmembrane-and cytoplasmic domains. In addition, certain viruses, especially those of the poxvirus family, contain genes encoding cytokine-binding proteins which are structurally similar in most cases to the sCR for particular cytokines. Such “viral sCRs” enhance the virulence of the virus by competing for binding of the cognate cytokine with its specific cell-membrane receptor, thus reducing any antiviral effects of the cytokine. The role of naturally produced, non-viral, sCRs seems less obvious, but since they retain their ability to fully bind their respective cognate cytokine, they too could effectively neutralise cytokine action by preventing the normal binding to cell surface receptors. Such sCR activity appears to be important during acute and chronic inflammatory conditions, where raised levels of certain sCRs have been reported[2, 3].

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  1. Division of Immunobiology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK

    Anthony Meager

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  1. Celltech Chiroscience, 216 Bath Road, Slough Berkshire, SL1 4EN, UK

    Gerry A. Higgs

  2. Cellular Microbiology Research Group Eastman Dental Institute, University College London, 256 Gray’s Inn Road, London, WC1X 8LD, UK

    Brian Henderson

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Meager, A. (2000). Blockade of cytokine activity by soluble cytokine receptors. In: Higgs, G.A., Henderson, B. (eds) Novel Cytokine Inhibitors. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8450-1_8

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  • DOI: https://doi.org/10.1007/978-3-0348-8450-1_8

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