The role of migrating leukocytes in IL-1 beta-induced up-regulation of kinin B(1) receptors in rats

Br J Pharmacol. 2002 Mar;135(5):1107-14. doi: 10.1038/sj.bjp.0704488.


1. The present study examines the role of migrating leukocytes in the ability of IL-1 beta to induce the functional up-regulation of B(1) receptors, as assessed by kinin B(1) agonist-induced oedema in the rat paw. 2. Pre-treatment with the PAF receptor antagonist WEB 2086 inhibited des-Arg(9)-BK-induced oedema in IL-1 beta-treated paws, while the LTB(4) receptor antagonist CP105696 had no effect. Des-Arg(9)-BK-induced paw oedema was also inhibited by pre-treatment with the selectin blocker fucoidin or by an anti-CD-18 monoclonal antibody. 3. I.d. injection of IL-1 beta produced a 5 - 10-fold increase of myeloperoxidase (MPO) activity in the rat paw. The increase in MPO activity was significantly inhibited by WEB 2086 (46 +/- 9%), fucoidin (68 +/- 5%) or the CD-18 antibody (84 +/- 3%). In contrast, i.d. injection of TNF alpha a dose known to upregulate the B(1) receptor functionally did not induce any significant increase in MPO activity. 4. Des-Arg(9)-BK alone had no effect in MPO activity but enhanced (by about 40%) the response induced by IL-1 beta, an effect prevented by the B(1) receptor antagonist des-Arg(9)-[Leu(8)]-BK. 5. The concentration of TNF-alpha was increased in the paws after i.d. injection of IL-1 beta. Pre-treatment with fucoidin, WEB 2086, anti-CD-18 or CP 105695, significantly reversed the local increases in TNF-alpha concentrations (80 +/- 2; 75 +/- 4, 73 +/- 3 and 40 +/- 2%), respectively. 6. Finally, IL-1 beta induced an increase of B(1) receptor mRNA levels in the rat paw, an effect which was prevented by fucoidin treatment. 7. Taken together, these results indicate that up-regulation of B(1) receptors in the rat paw following IL-1 beta seems to involve the local recruitment of neutrophils and subsequent local TNF-alpha production. The cross-talk between kinins, cytokines and leukocytes implicate B(1) receptors in chronic inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bradykinin Receptor Antagonists
  • Cell Adhesion Molecules
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / physiology*
  • Edema / metabolism
  • Injections, Intradermal
  • Interleukin-1 / pharmacology*
  • Male
  • Neutrophils / physiology
  • Peroxidase / metabolism
  • Platelet Membrane Glycoproteins / antagonists & inhibitors*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Receptor Cross-Talk
  • Receptor, Bradykinin B1
  • Receptors, Bradykinin / agonists
  • Receptors, Bradykinin / metabolism*
  • Receptors, Cell Surface*
  • Receptors, G-Protein-Coupled*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation*


  • Bradykinin Receptor Antagonists
  • Cell Adhesion Molecules
  • Interleukin-1
  • Platelet Membrane Glycoproteins
  • RNA, Messenger
  • Receptor, Bradykinin B1
  • Receptors, Bradykinin
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Tumor Necrosis Factor-alpha
  • platelet activating factor receptor
  • Peroxidase