Methods for treating and preventing fibrosis
The present invention provides methods of screening for compositions useful for treating, ameliorating, or preventing fibrosis and/or fibrosis-associated conditions by measuring changes in the level(s) of IL-21 and/or IL-21 receptor (IL-21R) (e.g., the level of expression of IL-21 and/or IL-21R protein and/or mRNA, the level of activity of IL-21 and/or IL-21R, the level of interaction of IL-21 with IL-21R). The invention further provides antagonists of IL-21 or IL-21R for the treatment of fibrosis and/or fibrosis-associated conditions. Further provided herein are methods of diagnosing, prognosing, and monitoring the progress (e.g., the course of treatment) of fibrosis and/or fibrosis-associated conditions by measuring the level of IL-21 and/or IL-21R (i.e., the level of activity of IL-21 and/or IL-21R, the level of expression of IL-21 and/or IL-21R (e.g., the level of IL-21 and/or IL-21R gene products), and/or the level of interaction of IL-21 with IL-21R).
1. A method for treating or ameliorating fibrosis or a fibrosis-associated disorder in a subject comprising administering to the subject a therapeutically effective amount of an agent that reduces the level of IL-21 and/or IL-21R in the subject, wherein the agent is an IL-21/IL-21R antagonist selected from the group consisting of an anti-IL-21R antibody, an anti-IL-21 antibody, an antigen-binding fragment of an anti-IL-21R antibody, and an antigen-binding fragment of an anti-IL-21 antibody.
2. The method of claim 1 , wherein the fibrosis or fibrosis-associated disorder affects the liver, epidermis, endodermis, muscle, tendon, cartilage, heart, pancreas, lung, uterus, nervous system, testis, ovary, adrenal gland, artery, vein, colon, small intestine, biliary tract, or stomach.
3. The method of claim 2 , wherein the fibrosis or fibrosis-associated disorder affects the liver, epidermis, endodermis, or lung.
4. The method of claim 3 , wherein the fibrosis or fibrosis-associated disorder is interstitial lung fibrosis.
5. The method of claim 2 , wherein the fibrosis or fibrosis-associated disorder is the result of an infection with schistosoma.
6. The method of claim 1 , wherein the fibrosis or fibrosis-associated disorder is the result of wound healing.
7. The method of claim 6 , wherein the wound healing results from a surgical incision.
8. The method of claim 1 , wherein the subject is a human.