INHIBITION OF INFLAMMATION USING ALPHA 7 RECEPTOR-BINDING CHOLINERGIC AGONISTS

摘要

Methods of inhibiting release of a proinflammatory cytokine from a macrophag e are provided. The methods comprise treating the macrophage with a cholinergi c agonist in an amount sufficient to decrease the amount of the proinflammator y cytokine that is released from the macrophage, wherein the cholinergic agoni st is selective for an .alpha.7 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 .alpha.7 nicotinic receptor. Methods for determining whether a compound is a cholinergic agonist reactive with an .alpha.7 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 whethe r a compound is a cholinergic antagonist reactive with an .alpha.7 nicotinic receptor are provided. These methods comprise determining whether the compou nd 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 attenuationof 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 .alpha.7 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.