Inhibition of lipopolysaccharide/ATP-induced release of interleukin-18 by KN-62 and glyburide.

Article Details

Citation

Copy to clipboard

Muhl H, Hofler S, Pfeilschifter J

Inhibition of lipopolysaccharide/ATP-induced release of interleukin-18 by KN-62 and glyburide.

Eur J Pharmacol. 2003 Dec 15;482(1-3):325-8.

PubMed ID

14660039 [ View in PubMed

]

Abstract

Monocytes 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glyburide	ATP-binding cassette sub-family A member 1	Protein	Humans	Unknown	Inhibitor	Details