ETH615, a synthetic inhibitor of leukotriene biosynthesis and function, also inhibits the production of and biological responses towards interleukin-8

Exp Dermatol. 1993 Aug;2(4):165-70. doi: 10.1111/j.1600-0625.1993.tb00027.x.

Abstract

ETH615 (4-(2-quinolylmethoxy)-N-(3-fluorobenzyl-phenyl-amino-methyl -4- benzoic-acid), a synthetic inhibitor of leukotriene B4 production and activities, was tested for its effect on the production of and biological responses towards human interleukin-8. We found that ETH615 inhibits lipopolysaccharide-induced (LPS-induced) expression of interleukin-8 messenger-RNA (mRNA) and interleukin-8 production in human peripheral blood mononuclear cells. We also observed that ETH615 completely inhibited interleukin-8 as well as leukotriene B4 directed chemotaxis of human neutrophils in a dose-dependent manner. A moderate effect on fMLP-directed neutrophil chemotaxis was observed. Further, no significant effect on either interleukin-8, leukotriene B4 or fMLP-directed T-cell migration was observed. These results further support the concept of a cytokine-leukotriene regulatory circuit and encourage the establishment of clinical trials testing the effect of ETH615 on inflammatory skin diseases, which are characterized by high levels of interleukin-8 and leukotriene B4 in lesional skin.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Chemotaxis, Leukocyte / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / metabolism
  • Interleukin-8 / pharmacology
  • Leukotriene B4 / antagonists & inhibitors
  • Monocytes / drug effects
  • Monocytes / metabolism
  • N-Formylmethionine Leucyl-Phenylalanine / antagonists & inhibitors
  • Neutrophils / drug effects
  • Quinolines / pharmacology*
  • Recombinant Proteins / antagonists & inhibitors
  • T-Lymphocytes / drug effects
  • Transcription, Genetic / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-8
  • Quinolines
  • Recombinant Proteins
  • ETH 615
  • Leukotriene B4
  • N-Formylmethionine Leucyl-Phenylalanine