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ETH615, a synthetic inhibitor of leukotriene biosynthesis and function, also inhibits the production of and biological responses towards interleukin‐8
Author(s) -
Kristensen Mette,
Jinquan Tan,
Thomsen Mads K.,
Zachariae Claus,
Paludan Kirsten,
AhnfeltRonne Ian,
Matsushima Kouki,
ThestrupPedersen Kristian,
Larsen Christian G.
Publication year - 1993
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.1993.tb00027.x
Subject(s) - leukotriene b4 , chemotaxis , interleukin 8 , interleukin , cytokine , leukotriene , peripheral blood mononuclear cell , leukotriene c4 , lipopolysaccharide , chemistry , immunology , pharmacology , biology , inflammation , in vitro , biochemistry , receptor , asthma
ETH6I5 (4‐(2‐quinolylmethoxy)‐N‐(3‐fluorobenzyl‐phenyl‐amino‐methyl‐4‐benzoic‐acid), a synthetic inhibitor of leukotriene B 4 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 B 4 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 B 4 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 B 4 in lesional skin.