Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation
View Patent ↗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.
1. A method for treating an inflammatory disorder in a patient, the method comprising:
evoking a sustained decrease in a level of one or more pro-inflammatory cytokines over an untreated state in the patient without increasing the activity of a humoral anti-inflammatory mediator by directly electrically stimulating the patient's vagus nerve from an electrode on the patient's vagus nerve, wherein the patient's heart rate remains stable for 10 minutes after the vagus nerve is electrically stimulated.
2. The method of claim 1 , wherein electrically stimulating the patient's vagus nerve comprises stimulating for less than about 20 min.
3. The method of claim 2 , wherein the patient's vagus nerve is not electrically stimulated again for at least about 30 min.
4. The method of claim 1 , wherein the electrical stimulation of the patient's vagus nerve does not stimulate a corticosteroid or IL-I0 response.
5. The method of claim 1 , wherein electrically stimulating the patient's vagus nerve comprises electrically stimulating the patient's entire vagus nerve, including afferent and efferent nerves.
6. The method of claim 1 , further comprising repeating the electrically stimulation of the patient's vagus.
7. The method of claim 1 , wherein electrically stimulating the patient's vagus nerve comprises stimulating the vagus nerve with electrical stimulation having a voltage of at least 1 volt.
8. The method of claim 1 , wherein the disorder is selected from the group consisting of rheumatoid arthritis and Crohn's disease.
9. A method for treating an inflammatory disorder in a patient, the method comprising:
evoking a sustained decrease in a level of tumor necrosis factor (TNF) over an untreated state in the patient without increasing the activity of corticosteroid or IL-I0 by directly electrically stimulating the patient's vagus nerve from an electrode on the patient's vagus nerve, wherein the patient's heart rate remains stable for 10 minutes after the vagus nerve is electrically stimulated.
10. The method of claim 9 , wherein electrically stimulating the patient's vagus nerve does not stimulate a corticosteroid or IL-I0 response.
11. The method of claim 9 , wherein electrically stimulating the patient's vagus nerve comprises stimulating the patient's vagus nerve with electrical stimulation having a voltage of at least 1 volt.
12. The method of claim 9 , wherein the disorder is selected from the group consisting of rheumatoid arthritis and Crohn's disease.