Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2

Biochem Pharmacol. 2005 Feb 1;69(3):385-94. doi: 10.1016/j.bcp.2004.10.007. Epub 2004 Dec 9.


Repertaxin is a new non-competitive allosteric blocker of interleukin-8 (CXCL8/IL-8) receptors (CXCR1/R2), which by locking CXCR1/R2 in an inactive conformation prevents receptor signaling and human polymorphonuclear leukocyte (PMN) chemotaxis. Given the unique mode of action of repertaxin it was important to examine the ability of repertaxin to inhibit a wide range of biological activities induced by CXCL8 in human leukocytes. Our results show that repertaxin potently and selectively blocked PMN adhesion to fibrinogen and CD11b up-regulation induced by CXCL8. Reduction of CXCL8-mediated PMN adhesion by repertaxin was paralleled by inhibition of PMN activation including secondary and tertiary granule release and pro-inflammatory cytokine production, whereas PMN phagocytosis of Escherichia coli bacteria was unaffected. Repertaxin also selectively blocked CXCL8-induced T lymphocyte and natural killer (NK) cell migration. These data suggest that repertaxin is a potent and specific inhibitor of a wide range of CXCL8-mediated activities related to leukocyte recruitment and functional activation in inflammatory sites.

MeSH terms

  • CD11b Antigen / biosynthesis
  • Cell Adhesion / drug effects
  • Chemotaxis, Leukocyte / drug effects
  • Humans
  • Interleukin-8 / antagonists & inhibitors*
  • Neutrophil Activation / drug effects
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Receptors, Interleukin-8A / antagonists & inhibitors*
  • Receptors, Interleukin-8B / antagonists & inhibitors*
  • Sulfonamides / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • CD11b Antigen
  • Interleukin-8
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Sulfonamides
  • reparixin