DEVICE AND METHOD FOR INHIBITING RELEASE OF PRO-INFLAMMATORY MEDIATOR

• US 20060287678A1
• Filed: 08/29/2006
• Published: 12/21/2006
• Est. Priority Date: 10/01/2003
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Shafer, Lisa Lynn
• Granted Patent: US 7,769,442 B2
• Time in Patent Office: Days
• US Class Current: 607/2
• CPC Class Codes: A61N 1/0556 Cuff electrodes
• CPC Class Codes: A61N 1/0558 Anchoring or fixation means therefor
• CPC Class Codes: A61N 1/36017 with leads or electrodes penetrating the skin
• CPC Class Codes: A61N 1/36021 for treatment of pain
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/36071 Pain

Abstract

Stimulation of one or more neurons of the sympathetic nervous system, including the splenic nerve, to attenuate an immune response, including an inflammatory immune response, is discussed. Devices and systems to stimulate the sympathetic nervous system to attenuate an immune response are also discussed. Devices discussed include pulse generators and drug pumps. Systems are described as optionally having one or more sensors and operator instructions. In specific examples, stimulation of the splenic nerve of pigs with a pulse generator is shown to be safe and effective in attenuating a lipopolysaccharide-induced immune response.

Claims

1. A method for inhibiting release of a proinflammatory mediator from a mammalian cell, the method comprising:

identifying a mammalian subject suffering from, or at risk for, a disease or disorder mediated by a proinflammatory mediator; and

applying a stimulation signal to the subject in an amount effective to inhibit the release of the proinflammatory mediator, wherein the stimulation signal is applied to a splenic nerve, splenic neurovascular bundle, a periarterial splenic nerve, splenic peritoneum, splenic tissue, celiac plexus surrounding the celiac artery, celiac ganglia, aorticorenal ganglia, greater thoracic splanchnic nerves, lesser thoracic splanchnic nerves, least thoracic splanchinc nerves or a combination thereof.

2. The method of claim 1, wherein the proinflammatory mediator is a pro-inflammatory cytokine.

3. The method of claim 2, wherein the cytokine is selected from the group consisting of tumor necrosis factor alpha (TNFα

);

interleukin (IL)-1α

;

IL-1β

;

IL-2;

IL-5;

IL-6;

IL-8;

IL-15;

IL-18;

interferon (IFN-γ

);

platelet-activating factor (PAF);

Thromboxane;

soluble adhesion molecules;

vasoactive neuropeptides;

phospholipase A2;

Plasminogen activator inhibitor (PAI-1);

Free radical generation;

Neopterin;

CD14;

prostacyclin;

Neutrophil elastase;

Protein kinase;

Monocyte chemotactic proteins 1 and 2 (MCP-1, MCP-2);

macrophage migration inhibitory factor (MIF); and

high mobility group box protein 1 (HMGB-1).

4. The method of claim 2, wherein the proinflammatory cytokine is selected from the group consisting of TNF-α

;

HMGB-1;

IL-1; and

IL-6.

5. The method of claim 2, wherein the proinflammatory cytokine is TNF-α

.

6. The method of claim 1, wherein the pro-inflammatory mediator is a chemokine.

7. The method of claim 1, wherein the disease or disorder is selected from the group consisting of appendicitis, peptic, gastric and duodenal ulcers, peritonitis, pancreatitis, pseudomembranous colitis, acute ulcerative colitis, chronic ulcerative colitis and ischemic colitis, diverticulitis, epiglottitis, achalasia, cholangitis, cholecystitis, hepatitis, nosicomial infection, Crohn'"'"'s disease, inflammatory bowl disease, enteritis, Whipple'"'"'s disease, diabetes, asthma, allergy, anaphylactic shock, immune complex disease, organ ischemia, reperfusion injury, organ necrosis, hay fever, sepsis, septicemia, endotoxic shock, cachexia, hyperpyrexia, eosinophilic granuloma, granulomatosis, sarcoidosis, septic abortion, epididymitis, vaginitis, prostatitis, urethritis, bronchitis, emphysema, rhinitis, cystic fibrosis, pneumonitis, pelvic inflammatory disease, alvealitis, bronchiolitis, pharyngitis, pleurisy, sinusitis, influenza, respiratory syncytial virus infection, herpes infection, HIV infection, hepatitis B virus infection, hepatitis C virus infection, disseminated bacteremia, Dengue fever, candidiasis, malaria, filariasis, amebiasis, hydatid cysts, burns, dermatitis, dermatomyositis, urticaria, warts, wheals, vasulitis, cardiovascular disease, angiitis, endocarditis, arteritis, atherosclerosis, thrombophlebitis, pericarditis, myocarditis, myocardial ischemia, periarteritis nodosa, rheumatic fever, rheumatoid arthritis, Alzheimer'"'"'s disease, coeliac disease, congestive heart failure, adult respiratory distress syndrome, meningitis, encephalitis, multiple sclerosis, cerebral infarction, cerebral embolism, Guillane-Barre syndrome, neuritis, neuralgia, spinal cord injury, paralysis, uveitis, arthritides, arthralgias, osteomyelitis, fasciitis, Paget'"'"'s disease, gout, periodontal disease, rheumatoid arthritis, synovitis, Sjogren'"'"'s syndrome, myasthenia gravis, thryoiditis, systemic lupus erythematosus, lupus erythematosus, Addison'"'"'s disease, pernicious anemia, Goodpasture'"'"'s syndrome, Behcets'"'"'s syndrome, allograft rejection, graft-versus-host disease, Type I diabetes, ankylosing spondylitis, Berger'"'"'s disease, Type I diabetes, ankylosing spondylitis, spinal cord injury, Retier'"'"'s syndrome, Graves disease, and Hodgkins disease.

8. The method of claim 1, wherein the disease or disorder is selected from the group consisting of endotoxic shock, appendicitis, peptic, gastric and duodenal ulcers, peritonitis, pancreatitis, inflammatory bowl disease, acute ulcerative colitis, chronic ulcerative colitis, ischemic colitis, hepatitis, nosicomial infection, Crohn'"'"'s disease, diabetes, asthma, allergy, anaphylactic shock, arteriosclerosis, organ ischemia, reperfusion injury, organ necrosis, sepsis, septicemia, cachexia, septic abortion, disseminated bacteremia, burns, rheumatoid arthritis, Alzheimer'"'"'s disease, coeliac disease, congestive heart failure, adult respiratory distress syndrome, cardiovascular disease, multiple sclerosis, diabetes, spinal cord injury, allograft rejection and graft-versus-host disease.

9. The method of claim 1, wherein a peripheral tissue or organ served by the splenic nerve is stimulated directly.

10. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a splenic nerve.

11. The method of claim 10, wherein applying the stimulation signal to the splenic nerve comprises applying the stimulation signal to a substantially fully dissected splenic nerve or nerve bundles.

12. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a celiac plexus surrounding the celiac artery.

13. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a splenic neurovascular bundle.

14. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a periarterial splenic nerve.

15. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a splenic peritoneum.

16. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a celiac ganglia.

17. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to an aorticorenal ganglia.

18. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a greater thoracic splanchnic nerve.

19. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a lesser thoracic splanchnic nerve.

20. The method of claim 1, wherein applying the stimulation signal comprises applying the stimulation signal to a least thoracic splanchinc nerve.

21. The method of claim 1, further comprising stimulating a vagus nerve.