Method of treating interleukin-6-mediated inflammatory diseases

• US 20030229030A1
• Filed: 06/11/2002
• Published: 12/11/2003
• Est. Priority Date: 06/11/2002
• Status: Abandoned Application

• Current Assignee: Theoharis C. Theoharides
• Original Assignee: Theoharis C. Theoharides
• Inventors: Theoharides, Theoharis C.
• Application Number:
  US10/166,088
• Publication Number:
  US 20030229030A1
• Time in Patent Office: Days
• US Class Current: 514/27
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/525 Isoalloxazines, e.g. riboflavins, vitamin B2
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid

Abstract

The invention is a method of treating IL-6-mediated inflammatory diseases with flavonoid inhibitors of the production and secretion of IL-6 from human or animal mast or macrophage cells. The most effective flavonoid compounds include quercetin, kaempferol, myricetin and genistein, and these can be administered alone or in combination with S-adenosylmethionine, folic acid, interleukin-10 or a histamine-1 receptor antagonist such as azelastine.

Claims

1. A method of treating interleukin-6 (IL-6)-mediated inflammatory diseases in human and animal species, comprising the step of contacting in vivo mast cells or macrophage cells from said species with a flavonoid compound in a concentration and time scale effective to inhibit the production and secretion of IL-6 from said cells.

2. The method according to claim 1, wherein said flavonoid compound is selected from the group consisting of quercetin, kaempferol, genistein, and myricetin.

3. The method according to claim 1, wherein said flavonoid compounds are administered as a glycoside derivative.

4. The method according to claim 1, wherein said effective concentration of said flavonoid compound is contained in a dose of between 10 and 3,000 mg per 70 kilogram body weight per day.

5. The method according to claim 1, wherein said effective concentration of said flavonoid compound is contained in a dose of between 40 and 200 mg per 70 kilogram body weight per day.

6. The method according to claim 1, wherein said flavonoid compound is administered together with an amount of folic acid effective to prevent homocysteine elevations that are a risk factor for coronary artery disease.

7. The method according to claim 1, wherein said flavonoid compound is administered in combination with S-adenosylmethionine in an amount sufficient to accelerate the metabolism of homocysteine to cysteine.

8. The method according to claim 1, wherein said production and secretion of said IL-6 in said cells are stimulated by Corticotropin Releasing Hormone.

9. The method according to claim 1, wherein said production and secretion of said IL-6 in said cells are stimulated by anti-IgE antibody.

10. The method according to claim 1, wherein said production and secretion of said IL-6 in said cells is stimulated by interleukin-1.

11. The method according to claim 1, wherein said flavonoid compound is administered in combination with interleukin-10 (IL-10) in an amount sufficient to inhibit IL-6 production and secretion.

12. The method according to claim 11, wherein said IL-10 is administered at a dose of between 2 and 2000 ng per 70 kg body weight per day.

13. The method according to claim 1, wherein said flavonoid compound is administered in combination with azelastine in amounts effective to inhibit the production and secretion of of IL-6.

14. The method according to claim 13, wherein said effective amount of azelastine is between 2 and 100 mg per 70 mg body weight per day.

15. The method according to any one of claims 1-14, wherein said compounds are administered in an oral or parenteral form.

16. The method according to any one of claims 1-14, where said compounds are administered in a topical form selected from the group consisting of a cream, ointment or transdermal formulation.

17. The method according to claim 1, wherein said inflammatory disease is selected from the group charactered by elevated serum and tissue levels of IL-6 in the patient, consisting of autoimmune disorders, plasma cell neoplasias, inflammatory diseases of the skin such as alopecia, eczema, scleroderma, psoriasis, neurofibramotosis, and delayed pressure urticaria, migraines, rheumatoid arthritis, juvenile chronic arthritis, unstable angina and C-Reactive Protein-mediated inflammation of blood vessels such as atherosclerosis, coronary artery disease, congestive heart failure, and reperfusion ischemia, inflammatory bowel diseases, interstitial cystitis, multiple sclerosis, asthma, and systemic mystocytosis.