Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation
First Claim
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1. A method for treating inflammation by inhibiting an inflammatory cytokine cascade in a patient, wherein the method comprises:
- evoking a sustained inhibition of the patient'"'"'s inflammatory cytokine cascade by electrically stimulating the patient'"'"'s vagus nerve for a first duration, followed by a second duration during which the patient'"'"'s vagus nerve is not electrically stimulated, wherein the second duration is at least three times longer than the first duration,wherein at the end of the second duration the levels of inflammatory cytokines are inhibited by at least 20% over the untreated state, and wherein the patient'"'"'s heart rate remains stable for 10 minutes after the vagus nerve is electrically stimulated.
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Abstract
A method of inhibiting the release of a proinflammatory cytokine in a cell is disclosed. The method comprises treating the cell with a cholinergic agonist. The method is useful in patients at risk for, or suffering from, a condition mediated by an inflammatory cytokine cascade, for example endotoxic shock. The cholinergic agonist treatment can be effected by stimulation of an efferent vagus nerve fiber, or the entire vagus nerve.
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Citations
20 Claims
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1. A method for treating inflammation by inhibiting an inflammatory cytokine cascade in a patient, wherein the method comprises:
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evoking a sustained inhibition of the patient'"'"'s inflammatory cytokine cascade by electrically stimulating the patient'"'"'s vagus nerve for a first duration, followed by a second duration during which the patient'"'"'s vagus nerve is not electrically stimulated, wherein the second duration is at least three times longer than the first duration, wherein at the end of the second duration the levels of inflammatory cytokines are inhibited by at least 20% over the untreated state, and wherein the patient'"'"'s heart rate remains stable for 10 minutes after the vagus nerve is electrically stimulated. - View Dependent Claims (2, 3, 4, 5, 6, 7, 20)
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8. A method of inhibiting an inflammatory cytokine cascade of a patient, wherein the method comprises:
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evoking a sustained inhibition of the patient'"'"'s inflammatory cytokine cascade by electrically stimulating the patient'"'"'s vagus nerve for a first duration of 20 minutes or less, followed by a second duration during which the patient'"'"'s vagus nerve is not electrically stimulated, wherein the second duration is at least three times longer than the first duration, wherein at the end of the second duration the levels of inflammatory cytokines are inhibited by at least 20% over the untreated state, and wherein the patient'"'"'s heart rate remains stable for 10 minutes after the vagus nerve is electrically stimulated. - View Dependent Claims (9, 10, 11, 12, 13)
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14. A method of providing therapy to a patient suffering from a condition that causes an inflammatory cytokine cascade, the method comprising:
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electrically stimulating vagus nerve activity in an amount sufficient to induce sufficient secretion of a cholinergic agonist to inhibit the inflammatory cytokine cascade by at least 20% over the untreated state, wherein the patient'"'"'s heart rate remains stable for 10 minutes after the vagus nerve is electrically stimulated; and monitoring a marker of the patient'"'"'s inflammatory cytokine cascade. - View Dependent Claims (15, 16, 17, 18, 19)
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Specification