Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation

• US 20050125044A1
• Filed: 11/17/2004
• Published: 06/09/2005
• Est. Priority Date: 05/23/2000
• Status: Active Grant

• Current Assignee: The Feinstein Institutes For Medical Research
• Original Assignee: North Shore-Long Island Jewish Research Institute
• Inventors: Tracey, Kevin J.
• Granted Patent: US 8,914,114 B2
• Time in Patent Office: Days
• US Class Current: 607/45
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/3606 adapted for a particular treatment
• CPC Class Codes: A61N 1/36167 Timing, e.g. stimulation onset
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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.

Claims

1. A method for treating a patient suffering from, or at risk for, a condition mediated by the inflammatory cytokine cascade, wherein the method comprises stimulating vagus nerve activity in an amount sufficient to inhibit the inflammatory cytokine cascade and wherein the condition mediated by the inflammatory cytokine cascade is selected from the group consisting of appendicitis, ulcerative colitis, Crohn'"'"'s disease, allergy, organ ischemia, reperfusion injury, sepsis, endotoxic shock, allograft rejection, rheumatoid arthritis, systemic lupus erythematosus, pancreatitis, peritonitis, hepatitis, burns, Behcet'"'"'s syndrome, graft-versus-host disease, multiple sclerosis, atherosclerosis and cachexia.

2. The method of claim 1, wherein the method comprises stimulating efferent vagus nerve activity.

3. The method of claim 1, wherein the method comprises electrically stimulating vagus nerve activity.

4. The method of claim 2, wherein the method comprises electrically stimulating efferent vagus nerve activity.

5. The method of claim 1, wherein the method comprises mechanically stimulating vagus nerve activity.

6. The method of claim 5, wherein the method comprises mechanically stimulating efferent vagus nerve activity.

7. The method of claim 3, wherein vagus nerve activity is stimulated using a vagus nerve stimulator.

8. The method of claim 1, wherein the condition is appendicitis.

9. The method of claim 1, wherein the condition is ulcerative colitis.

10. The method of claim 1, wherein the condition is Crohn'"'"'s disease.

11. The method of claim 1, wherein the condition is allergy.

12. The method of claim 1, wherein the condition is organ ischemia.

13. The method of claim 1, wherein the condition is reperfusion injury.

14. The method of claim 1, wherein the condition is sepsis.

15. The method of claim 1, wherein the condition is endotoxic shock.

16. The method of claim 1, wherein the condition is allograft rejection.

17. The method of claim 1, wherein the condition is graft-versus-host disease.

18. The method of claim 1, wherein the condition is rheumatoid arthritis.

19. The method of claim 1, wherein the condition is systemic lupus erythematosus.

20. The method of claim 1, wherein the condition is pancreatitis.

21. The method of claim 1, wherein the condition is peritonitis.

22. The method of claim 1, wherein the condition is burns.

23. The method of claim 1, wherein the condition is Behcet'"'"'s disease.

24. The method of claim 1, wherein the condition is multiple sclerosis.

25. The method of claim 1, wherein the condition is cachexia.

26. The method of claim 1, wherein the condition is hepatitis.

27. The method of claim 1, wherein the condition is atherosclerosis.