Cardiac glycosides to treat cystic fibrosis and other IL-8 dependent disorders
OwnerBette Pollardinventor
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Abstract
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.
Claims16
A method of treating a patient in need of treatment for a disease condition caused or aggravated by an excessive level of IL-8, comprising administering a cardiac glycoside that lacks an oxygen-containing substituent at both C11 and C12 and has glycosyl moieties at the C3 position, wherein the cardiac glycoside is administered at a concentration of from about 1 nM to about 2 nM, adjusted to the mass of the recipient and the need of the recipient to inhibit or reduce the level of IL-8.
A method of treating a mammal in need of treatment for disease conditions characterized by elevated levels of IL-8, comprising administering an effective amount of a cardiac glycoside having glycosyl moieties at the C3 position and lacking an oxygen-containing substituent at both C11 and C12 wherein the effective amount is a concentration of from about 1 nM to about 2 nM, adjusted to the mass of the recipient and the need of the recipient to reduce or inhibit the level of IL-8.
A method for inhibiting or reducing the secretion of IL-8 from a cell secreting elevated levels of IL-8, comprising administering a cardiac glycoside in a concentration of from about 1 nM to about 2 nM, adjusted to the mass of the recipient and the need of the recipient to reduce or inhibit the level of IL-8, and wherein the cardiac glycoside has glycosyl moieties at the C3 position and lacks an oxygen-containing substituent at both C11 and C12.
Dependencies are inferred from the claim text.