Heiko Mühl, Sonja Höfler, Josef Pfeilschifter
Pharmazentrum frankfurt, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. H.Muehl@em.uni-frankfurt.de
European journal of pharmacology 2003 Dec 15Monocytes release interleukin-18 after activation by lipopolysaccharide/ATP. Since inflammatory conditions such as sepsis are characterized by augmented interleukin-18 in sera of patients, we sought to modulate lipopolysaccharide/ATP-induced interleukin-18 release by pharmacological means. Here we report that 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), an inhibitor of ATP-mediated cellular activation by the purinoreceptor subtype P(2x7), potently suppresses interleukin-18 release from peripheral blood mononuclear cells. Interleukin-18 liberation was likewise inhibited by glyburide, a modulator of ion transport and inhibitor of ATP-binding cassette transporter 1. The data presented herein indicate that by pharmacologically interfering with the process of cytokine secretion agents such as KN-62 or glyburide have the potential to curb overproduction of interleukin-18 in septic patients.
Heiko Mühl, Sonja Höfler, Josef Pfeilschifter. Inhibition of lipopolysaccharide/ATP-induced release of interleukin-18 by KN-62 and glyburide. European journal of pharmacology. 2003 Dec 15;482(1-3):325-8
PMID: 14660039
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