Antagonists of HMG1 for treating inflammatory conditions
View Patent ↗There is disclosed a pharmaceutical composition and method for treating sepsis, including, septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk or exhibit sepsis or septic shock symptoms. Lastly, there is disclosed a pharmaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.
1. A method for treating a condition characterized by activation of the inflammatory cytokine cascade, comprising administering an amount of an HMG1 antagonist effective to inhibit the inflammatory cytokine cascade, wherein said HMG1 antagonist is an antibody that binds to HMG1 and inhibits the interaction between HMG1 and RAGE.
2. The method of claim 1 further comprising administering a second agent in combination with the HMG1 antagonist, wherein the second agent is an antagonist of an early sepsis mediator.
3. The method of claim 2 wherein the second agent is an antagonist of a cytokine selected from the group consisting of TNF, IL-1α, IL-1β, MIF and IL-6.
4. The method of claim 3 wherein the second agent is an antibody to TNF or an IL-1 receptor antagonist.
5. A method for treating sepsis, comprising administering an amount of an HMG1 antagonist effective to inhibit the inflammatory cytokine cascade, wherein said HMG1 antagonist is an antibody that binds to HMG1 and inhibits the interaction between HMG1 and RAGE.
6. The method of claim 5 further comprising administering a second agent in combination with the HMG1 antagonist, wherein the second agent is an antagonist of an early sepsis mediator.
7. The method of claim 6 wherein the second agent is an antagonist of a cytokine selected from the group consisting of TNF, IL-1α, IL-1β, MIF and IL-6.
8. The method of claim 7 wherein the second agent is an antibody to TNF or an IL-1 receptor antagonist.
9. A method for treating rheumatoid arthritis, comprising administering an amount of an HMG1 antagonist effective to inhibit the inflammatory cytokine cascade, wherein said HMG1 antagonist is an antibody that binds to HMG1 and inhibits the interaction between HMG1 and RAGE.
10. The method of claim 9 further comprising administering a second agent in combination with the HMG1 antagonist, wherein the second agent is an antagonist of an early sepsis mediator.
11. The method of claim 10 wherein the second agent is an antagonist of a cytokine selected from the group consisting of TNF, IL-1α, IL-1β, MIF and IL-6.
12. The method of claim 11 wherein the second agent is an antibody to TNF or an IL-1 receptor antagonist.
13. A method for treating inflammatory bowel disease, comprising administering an amount of an HMG1 antagonist effective to inhibit the inflammatory cytokine cascade, wherein said HMG1 antagonist is an antibody that binds to HMG1 and inhibits the interaction between HMG1 and RAGE.
14. The method of claim 13 further comprising administering a second agent in combination with the HMG1 antagonist, wherein the second agent is an antagonist of an early sepsis mediator.
15. The method of claim 14 wherein the second agent is an antagonist of a cytokine selected from the group consisting of TNF, IL-1α, IL-1β, MIF and IL-6.
16. The method of claim 15 wherein the second agent is an antibody to TNF or an IL-1 receptor antagonist.
17. A method for treating systemic lupus erythematosus, comprising administering an amount of an HMG1 antagonist effective to inhibit the inflammatory cytokine cascade, wherein said HMG1 antagonist is an antibody that binds to HMG1 and inhibits the interaction between HMG1 and RAGE.
18. The method of claim 17 further comprising administering a second agent in combination with the HMG1 antagonist, wherein the second agent is an antagonist of an early sepsis mediator.
19. The method of claim 18 wherein the second agent is an antagonist of a cytokine selected from the group consisting of TNF, IL-1α, IL-1β, MIF and IL-6.
20. The method of claim 19 wherein the second agent is an antibody to TNF or an IL-1 receptor antagonist.
21. A method for treating psoriasis, comprising administering an amount of an HMG1 antagonist effective to inhibit the inflammatory cytokine cascade, wherein said HMG1 antagonist is an antibody that binds to HMG1 and inhibits the interaction between HMG1 and RAGE.
22. The method of claim 21 further comprising administering a second agent in combination with the HMG1 antagonist, wherein the second agent is an antagonist of an early sepsis mediator.
23. The method of claim 22 wherein the second agent is an antagonist of a cytokine selected from the group consisting of TNF, IL-1α, IL-1β, MIF and IL-6.
24. The method of claim 23 wherein the second agent is an antibody to TNF or an IL-1 receptor antagonist.
25. A method for treating cardiovascular disease, comprising administering an amount of an HMG1 antagonist effective to inhibit the inflammatory cytokine cascade, wherein said HMG1 antagonist is an antibody that binds to HMG1 and inhibits the interaction between HMG1 and RAGE.
26. The method of claim 25 further comprising administering a second agent in combination with the HMG1 antagonist, wherein the second agent is an antagonist of an early sepsis mediator.
27. The method of claim 26 wherein the second agent is an antagonist of a cytokine selected from the group consisting of TNF, IL-1α, IL-1β, MIF and IL-6.
28. The method of claim 27 wherein the second agent is an antibody to TNF or an IL-1 receptor antagonist.