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AssigneeNorth Shore-Long Island Jewish Research Institute
InventorsKevin J. Tracey, Hong Wang
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Methods of inhibiting release of a proinflammatory cytokine from a macrophage are provided. The methods comprise treating the macrophage with a cholinergic agonist in an amount sufficient to decrease the amount of the proinflammatory cytokine that is released from the macrophage, wherein the cholinergic agonist is selective for an α7 nicotinic receptor. Methods for inhibiting an inflammatory cytokine cascade in a patient are also provided. The methods comprise treating the patient with a cholinergic agonist in an amount sufficient to inhibit the inflammatory cytokine cascade, wherein the cholinergic agonist is selective for an α7 nicotinic receptor. Methods for determining whether a compound is a cholinergic agonist reactive with an α7 nicotinic receptor are also provided. The methods comprise determining whether the compound inhibits release of a proinflammatory cytokine from a mammalian cell. Additionally, methods for determining whether a compound is a cholinergic antagonist reactive with an α7 nicotinic receptor are provided. These methods comprise determining whether the compound reduces the ability of a cholinergic agonist to inhibit the release of a proinflammatory cytokine from a mammalian cell. Oligonucleotides or mimetics capable of inhibiting attenuation of lipopolysaccharide-induced TNF release from a mammalian macrophage upon exposure of the macrophage to a cholinergic agonist are also provided. The oligonucleotides or mimetics consist essentially of a sequence greater than 5 nucleotides long that is complementary to an mRNA of an α7 receptor. Additionally, methods of inhibiting attenuation of TNF release from a mammalian macrophage upon exposure of the macrophage to a cholinergic agonist are provided. These methods comprise treating the macrophage with the above-described oligonucleotide or mimetic.
A method of treating a patient suffering from a condition mediated by release of a proinflammatory cytokine comprising
A method for determining whether a compound is a cholinergic agonist selective for an α7 nicotinic receptor, the method comprising
A method for determining whether a compound is a cholinergic antagonist reactive with an α7 nicotinic receptor, the method comprising determining whether the compound reduces the ability of a cholinergic agonist to inhibit the release of a proinflammatory cytokine from a mammalian cell,
A method for determining whether a test compound has the ability to inhibit inflammation, the method comprising determining whether the test compound is a cholinergic agonist reactive with an α7 nicotinic receptor.
A method for determining whether a test compound has the ability to inhibit inflammation, the method comprising determining whether the test compound inhibits binding of an antagonist to an α7 nicotinic receptor.
An oligonucleotide or mimetic capable of inhibiting attenuation of lipopolysaccharide-induced TNF release from a mammalian macrophage upon exposure of the macrophage to a cholinergic agonist, wherein the oligonucleotide or mimetic consists essentially of a sequence greater than 5 nucleotides long that is complementary to an mRNA of an α7 receptor.
Dependencies are inferred from the claim text.