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IL-8 receptor antagonist: basic research and clinical utility

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Chemokine Biology — Basic Research and Clinical Application

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

Abstract

Inflammatory cells are thought to be instrumental in the pathophysiology of diseases and the control of their recruitment and activation appears to be an attractive strategy for therapeutic intervention. Chemokines are a family of small molecular weight (7–15 kDa) proteins that in conjunction with adhesion molecules play a crucial role in leukocyte recruitment, cellular activation and proliferation at sites of inflammation. Chemokines are produced by a variety of cell types, including leukocytic and non-leukocytic cells, usually in response to antigens, irritants and other cytokines. Interleukin-8 (CXCL8) was the first member to be identified of this new family of proinflammatory chemokines that now constitute over 45 members. Chemokines produce their biological effects by interacting with greater than 18 G protein coupled cell surface receptors. A few chemokines bind selectively to a single receptor but other chemokines bind to more than one receptor [1, 2]. CXCL8 belongs to a subgroup of chemokines known as ELR+ chemokines because of the Glu4-Leu5-Arg6 amino acid sequence between positions 4 and 6. Other members of this group include CXCL1, 2, 3, 5, 6, and 7. A diverse variety of biological effects are attributed to CXCL8 and related ELR+ chemokines, including several involving inflammatory cell activation and chemotaxis, production of reactive oxygen species, increased expression of the integrin CD11b-CD18, enhancement of cell adhesion to endothelial cells, promotion of angiogenesis, modulation of histamine and lipid mediator release as well as azurophil granule release [3].

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Authors and Affiliations

  1. Biopharmaceutical CEDD, GlaxoSmithKline, P.O. Box 1539, King of Prussia, PA, 19406, USA

    John R. White

  2. Respiratory and Inflammation CEDD, GlaxoSmithKline, P.O. Box 1539, King of Prussia, PA, 19406, USA

    Henry M. Sarau

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  1. John R. White
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Editors and Affiliations

  1. Lilly Corporate Center, Cancer Inflammation and Cell Survival Eli Lilly and Company, Indianapolis, IN, 46285, USA

    Kuldeep Neote

  2. NitroMed, Inc., 12 Oak Park Drive, Bedford, MA, 01730, USA

    Gordon L. Letts

  3. Theodor Koch Institute, University of Bern, Freiestrasse 1, 3012, Bern, Switzerland

    Bernhard Moser

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White, J.R., Sarau, H.M. (2007). IL-8 receptor antagonist: basic research and clinical utility. In: Neote, K., Letts, G.L., Moser, B. (eds) Chemokine Biology — Basic Research and Clinical Application. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7437-2_7

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