ETH615, a synthetic inhibitor of leukotriene biosynthesis and function, also inhibits the production of and biological responses towards interleukin-8.
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.
Kristensen
M
M
Department of Dermatology, Marselisborg University Hospital, University of Aarhus, Denmark.
Jinquan
T
T
Thomsen
M K
MK
Zachariae
C
C
Paludan
K
K
Ahnfelt-Rønne
I
I
Matsushima
K
K
Thestrup-Pedersen
K
K
Larsen
C G
CG
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016209:Interleukin-8; D011804:Quinolines; D011994:Recombinant Proteins; C069967:ETH 615; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine