Potent and specific inhibition of IL-8-, IL-1 alpha- and IL-1 beta-induced in vitro human lymphocyte migration by calcium channel antagonists

Biochem Biophys Res Commun. 1989 Nov 30;165(1):349-54. doi: 10.1016/0006-291x(89)91076-0.

Abstract

The role of calcium in interleukin- (IL) 8-, IL-1 alpha- and IL-1 beta-induced lymphocyte migration has been investigated by using the calcium channel antagonists, verapamil, nifedipine, diltiazem (IL-8) and the optical isomers of the dihydropyridine analogue SDZ 202-791 (IL-8, IL-1 alpha and IL-1 beta). Potent inhibition of IL-8-induced migration was observed in response to nifedipine (IC50 = 10 nM), verapamil (IC50 = 60 nM) and diltiazem (IC50 = 10 nM). The (+)-isomer of SDZ 202-791 was without effect on any of the agonists tested, however, the (-)-isomer induced dose-related inhibition of stimulated migration, IC50 values being 0.1 nM, 10 pM and 1.0 nM, for IL-8-, IL-1 alpha- and IL-1 beta-induced migration, respectively. Reversal of the inhibitory effects of the (-)-isomer was obtained in the presence of increasing concentrations of (+)-isomer. The induction of lymphocyte migration by IL-8, IL-1 alpha and IL-1 beta therefore appears to be a process dependent on calcium channel activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Channel Blockers / pharmacology*
  • Chemotactic Factors / pharmacology*
  • Chemotaxis, Leukocyte / drug effects*
  • Dihydropyridines / pharmacology
  • Diltiazem / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • Interleukin-1 / pharmacology*
  • Interleukin-8
  • Interleukins / pharmacology*
  • Kinetics
  • Lymphocytes / drug effects
  • Lymphocytes / physiology*
  • Nifedipine / pharmacology
  • Recombinant Proteins / pharmacology
  • Verapamil / pharmacology

Substances

  • Calcium Channel Blockers
  • Chemotactic Factors
  • Dihydropyridines
  • Interleukin-1
  • Interleukin-8
  • Interleukins
  • Recombinant Proteins
  • SAN 202791
  • Verapamil
  • Diltiazem
  • Nifedipine