Method of treating diseases associated with elevated levels of interleukin 1

• US 5,162,361 A
• Filed: 04/10/1990
• Issued: 11/10/1992
• Est. Priority Date: 04/10/1990
• Status: Expired due to Term

• Current Assignee: The United States of America As Represented By The Secretary of Agriculture
• Original Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Inventors: Taylor, Michael, Rosenthal, Gary J., Craig, William, Luster, Michael, Blaylock, Benny, Corsini, Emanuela, Comment, Christine, Kouchi, Yasuhida
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US07/506,613
• Time in Patent Office: 945 Days
• Field of Search: 514/396, 514/397, 514/398, 514/399, 514/400, 514/401, 514/825, 514/863, 514/885, 514/886, 424/45
• US Class Current: 514/396
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/415 1,2-Diazoles

Abstract

The present invention relates to a method of treating diseases associated with elevated levels of interleukin 1 (IL-1) including inflammatory diseases such as arthritis, skin hypersensitivity and endotoxemia. More specifically, the invention relates to a method for the treatment of such diseases in warm-blooded animals, such as humans, which comprises the administration of a therapeutically effective amount of an aromatic diamidine, sufficient to inhibit IL-1 release from IL-1 producing cells. The aromatic diamidine can also be used to block interleukin 6 (IL-6) and tumor necrosis factor from cells producing these cytokines.

Claims

1. A method for inhibiting the release of interleukin 1 from interleukin 1 producing cells, comprising contacting said cells with an amount of an aromatic diamidine sufficient to inhibit interleukin 1 release from said cells, wherein said cells are in a human afflicted with an inflammatory disease or condition selected from the group consisting of arthritis, skin hypersensitivity, glomerulonephritis, septicemia, endotoxemia, pulmonary granulomas, pulmonary fibrosis, cirrhosis, sarcoidosis, tuberculosis, chronic granulomatous disease, dysfunctional clot formation and transplant rejection, and diseases and conditions associated with the release of acute phase reactants by hepatocytes.

2. The method of claim 1, wherein the aromatic diamidine is administered to the human in the form of an aerosol.

3. The method of claim 2, wherein the aromatic diamidine is administered to the human in the form of an aerosol at a dosage of up to 650 mg per dose of active ingredient.

4. The method of claim 3, wherein the aromatic diamidine is administered to the human at a dosage of about 300 mg per dose.

5. The method of claim 1, wherein the aromatic diamidine is injected in the human.

6. The method of claim 5, wherein the aromatic diamidine is injected in the human at a dosage of up to 15 mg active ingredient/kg human.

7. The method of claim 5, wherein the aromatic diamidine is injected in the human subcutaneously.

8. The method of claim 5, wherein the aromatic diamidine is injected in the human intrasmuscularly.

9. The method of claim 1, wherein the aromatic diamidine is administered in the human dermally.

10. The method of claim 9, wherein the aromatic diamidine is administered to the human dermally at a concentration of up to 1% active ingredient in solution.

11. The method of claim 1, wherein the inflammatory disease is arthritis.

12. The method of claim 1, wherein the inflammatory disease is a hypersensitivity disease.

13. The method of claim 1, wherein the inflammatory disease is endotoxemia.

14. A method for inhibiting release of interleukin 1 from interleukin 1 producing cells, comprising contacting said cells with an amount of an aromatic diamidine sufficient to inhibit the interleukin 1 release from said cells.

15. The method of claim 14, wherein the aromatic diamidine is 1,5-bis(4-amidinophenoxy)pentane.

16. The method of claim 15, wherein the 1,5-bis(4-amidinophenoxy)pentane is in the form of pentamidine isethionate.

17. The method of claim 14, wherein the aromatic diamidine is an imidazoline.

18. The method of claim 17, wherein the imidazoline is in the form of 1,5-di(4-imidazolinophenoxy)pentane.

19. A method for inhibiting release of tumor necrosis factor from tumor necrosis factor producing cells, comprising contacting said cells with an amount of an aromatic diamidine sufficient to inhibit the tumor necrosis factor release from said cells.

20. The method of claim 19, wherein the aromatic diamidine is 1,5-bis(4-amidinophenoxy)pentane.

21. The method of claim 20, wherein the 1,5-bis(4-amidinophenoxy)pentane is in the form of pentamidine isethionate.

22. The method of claim 19, wherein the aromatic diamidine is an imidazoline.

23. The method of claim 22, wherein the imidazoline is in the form of 1,5-di(4-imidazolinophenoxy)pentane.

24. A method for inhibiting release of interleukin 6 from interleukin 6 producing cells, comprising contacting said cells with an amount of an aromatic diamidine sufficient to inhibit the interleukin 6 release from said cells.

25. The method of claim 24, wherein the aromatic diamidine is 1,5-bis(4-amidinophenoxy)pentane.

26. The method of claim 25, wherein the 1,5-bis(4-amidinophenoxy)pentane is in the form of pentamidine isethionate.

27. The method of claim 24, wherein the aromatic diamidine is an imidazoline.

28. The method of claim 27, wherein the imidazoline is in the form of 1,5-di(4-imidazolinophenoxy)pentane.