Methods of lowering serum cholesterol
Methods of treating subjects having diseases, disorders, or conditions, including disorders associated with cholesterol homeostasis, responsive to agents modulating Kupffer cell function, including methods of administration and dosing regimens associated therewith, are provided. Methods of treating subjects having liver diseases, disorders, or conditions, including non-alcoholic steatohepatitis and non-alcoholic fatty liver disease, with an IL-10 agent are also provided.
1. A method of treating non-alcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD) in a subject, the method comprising: administering parenterally to a subject having NASH or NAFLD a therapeutically effective amount of a composition comprising a PEGylated interleukin-10 (PEG-IL-10) agent, wherein the amount is sufficient to maintain an IL-10 serum trough concentration from 1.0 pg/mL to 10.0 ng/mL, over a period of time of at least 24 hours.
2. The method of claim 1 , wherein the PEG-IL-10 agent comprises mature human IL-10.
3. The method of claim 1 , wherein the PEG-IL-10 agent comprises a variant of mature human IL-10, and wherein the variant exhibits activity comparable to the activity of mature human IL-10.
4. The method of claim 1 , wherein said administering is effective to decrease cholesterol in the subject.
5. The method of claim 1 , wherein said administering is effective to decrease triglycerides in the subject.
6. The method of claim 1 , wherein said administering is effective to decrease peri-portal collagen deposition in the subject.
7. The method of claim 1 , wherein said administering is effective to increase hepatocyte proliferation in the subject.
8. The method of claim 1 , wherein said administering is subcutaneous.
9. The method of claim 1 , wherein the method comprises administering at least one additional prophylactic or therapeutic agent.
10. The method of claim 1 , wherein the PEG-IL-10 agent comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one subunit of IL-10.
11. The method of claim 1 , wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.
12. The method of claim 1 , wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa to about 20 kDa.
13. The method of claim 1 , wherein the PEG component of the PEG-IL-10 agent has a molecular mass greater than about 20 kDa.
14. The method of claim 1 , wherein the PEG component of the PEG-IL-10 agent has a molecular mass of at least about 30 kD.
15. The method of claim 1 , wherein the subject is a human.
16. A method of treating hypercholesterolemia or a hypercholesterolemia-associated disease, disorder or condition in a subject having non-alcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD), the method comprising: administering parenterally to the subject a composition comprising PEGylated interleukin-10 (PEG-IL-10) agent and a composition comprising ezetimibe,
wherein said administering is effective to reduce cholesterol in the subject and wherein the amount is sufficient to maintain an IL-10 serum trough concentration from 1.0 pg/mL to 10.0 ng/mL, over a period of time of at least 24 hours.
17. The method of claim 16 , wherein the composition comprising PEG-IL-10 and the composition comprising a ezetimibe are administered sequentially.
18. The method of claim 16 , wherein the PEG-IL-10 agent comprises mature human IL-10.
19. The method of claim 16 , wherein the PEG-IL-10 agent comprises a variant of mature human IL-10, and wherein the variant exhibits activity comparable to the activity of mature human IL-10.
20. The method of claim 16 , wherein said administering of the composition comprising the PEG-IL-10 agent is subcutaneous.
21. The method of claim 16 , wherein the PEG-IL-10 agent comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one subunit of IL-10.
22. The method of claim 16 , wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.
23. The method of claim 16 , wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa to about 20 kDa.
24. The method of claim 16 , wherein the PEG component of the PEG-IL-10 agent has a molecular mass greater than about 20 kDa.
25. The method of claim 16 , wherein the PEG component of the PEG-IL-10 agent has a molecular mass of at least about 30 kD.
26. The method of claim 16 , wherein the subject is a human.