Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha

J Clin Invest. 1997 Dec 1;100(11):2752-6. doi: 10.1172/JCI119821.


Endothelial cells initiate the inflammatory response by recruiting and activating leukocytes. IL-6 is not an agonist for this, but we found soluble IL-6 receptor alpha-subunit (IL-6Ralpha), with their constitutive IL-6 synthesis, stimulated endothelial cells to synthesize E-selectin, intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, IL-6, and IL-8, and to bind neutrophils. Neutrophils express significant amounts of IL-6Ralpha and upon stimulation shed it: this material activates endothelial cells through a newly constituted IL-6 receptor. Retrograde signaling from PMN activated in the extravascular compartment to surrounding endothelial cells will recruit more and a wider variety of leukocytes. The limiting signal is a soluble receptor, not a cytokine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • E-Selectin / biosynthesis
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Inflammation
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Rabbits
  • Receptors, Interleukin-6 / biosynthesis
  • Receptors, Interleukin-6 / metabolism*
  • Signal Transduction*
  • Solubility
  • Vascular Cell Adhesion Molecule-1 / biosynthesis


  • E-Selectin
  • Interleukin-6
  • Interleukin-8
  • Receptors, Interleukin-6
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1