Cardiac glycosides to treat cystic fibrosis and other il-8...

Details Cardiac glycosides to treat cystic fibrosis and other il-8... Cardiac glycosides to treat cystic fibrosis and other il-8...

A - Human Necessities

61

K

A61K 31/704 (2006.01) A61K 31/585 (2006.01) A61K 31/7048 (2006.01)

Patent

CA 2487732

A method of inhibiting the secretion of IL-8 and other pro-inflammatory cytokines from cells secreting elevated levels of these compounds is provided. The method includes contacting the cell with a composition comprising a cardiac glycoside such as oleandrin. The cardiac glycoside can be used to treat cystic fibrosis and other IL-8 dependent disorders by lowering levels of spontaneously secreted IL-8 and other pro-inflammatory cytokines. Oleandrin was found to suppress the secretion of IL-8 from cultured CF lung epithelial cells in the nanomolar concentration range. Structure-activity relationships (SARs) for cardiac glycosides are also elucidated.

Cette invention concerne une méthode propre à inhiber la sécrétion de IL-8 et autres cytokines pro-inflammatoires par des cellules qui sécrètent des niveaux élevés de ces composés. Cette méthodes consiste à mettre la cellule en contact avec un glucoside cardiotonique telle que l'oléandrine. Le glucoside cardiotonique peut s'utiliser pour le traitement de la mucovicidose (CF) et autres troubles dépendant de IL-8, par abaissement des niveaux de IL-8 sécrété spontanément et autres cytokines pro-inflammatoires. On a constaté que l'oléandrine supprimait la sécrétion de IL-8 à partir de cellules épithéliales pulmonaires CF cultivées dans la plage de concentration nanomolaire. les rapports structure-activité (SAR) ont également été élucidés pour les glucosides cardiotoniques.

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