Methods of use for il-22 in the treatment of gastrointestinal graft vs. host disease

Abstract

The present invention provides methods and compositions for the use of IL-22 for treating conditions of intestinal injury and inflammatory conditions such as graft vs. host disease. Specifically, IL-22 can be used to increase Intestinal Stem Cell (ISC) recovery and for enhancing immune reconstitution following allogeneic hematopoietic transplantation. In particularly preferred embodiments, the present invention provides methods of using therapeutic IL-22, including a dimeric form of IL-22, in therapeutic compositions for treating graft vs. host disease, including hepatic, thymic, gastrointestinal, or other graft vs. host disease in hematopoietic stem cell transplant patients and in patients with inflammatory intestinal conditions.

1 . A method to promote the recovery/regeneration of gastrointestinal (GI) epithelial cells in a subject following injury or damage to the gastrointestinal tract, the method comprising contacting intestinal stem cells (ISC) of the subject with interleukin-22 (IL-22). 
     
     
         2 . (canceled) 
     
     
         3 . A method for enhancing the proliferation of intestinal stem cells (ISC), the method comprising contacting said ISC with exogenous IL-22 under conditions to promote growth of ISC. 
     
     
         4 - 17 . (canceled) 
     
     
         18 . A method for treating gastrointestinal graft versus host disease (GVHD) in a subject, the method comprising injecting the subject with a therapeutically effective amount of an interleukin-22 (IL-22), wherein the subject is an allo-hematopoietic stem cell transplant recipient, and the IL-22 amino acid sequence is selected from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5. 
     
     
         19 . The method of  claim 18 , wherein the therapeutically effective amount of IL-22 is administered to the subject before transplant. 
     
     
         20 . The method of  claim 18 , wherein the therapeutically effective amount of IL-22 is administered to the subject once onset of symptoms associated with injury to the gastrointestinal tract is observed. 
     
     
         21 . The method of  claim 18 , wherein the therapeutically effective amount of IL-22 is administered to the subject from 1 day to 6 months following transplant. 
     
     
         22 . The method of  claim 18 , wherein the therapeutically effective amount of IL-22 is administered to the subject beginning from 1 week to 4 months following transplant. 
     
     
         23 . The method of  claim 18 , wherein the IL-22 is administered daily. 
     
     
         24 . The method of  claim 18 , further comprising co-administering an immunosuppressive agent to the subject. 
     
     
         25 . The method of  claim 18 , further comprising co-administering prednisone to the subject. 
     
     
         26 . The method of  claim 18 , wherein the IL-22 amino acid sequence is SEQ ID NO: 2. 
     
     
         27 . The method of  claim 26 , wherein the IL-22 is in the form of an IL-22 dimer. 
     
     
         28 . The method of  claim 18 , wherein the IL-22 amino acid sequence is SEQ ID NO: 3. 
     
     
         29 . The method of  claim 28 , wherein the IL-22 is in the form of an IL-22 dimer. 
     
     
         30 . The method of  claim 18 , wherein the IL-22 amino acid sequence is SEQ ID NO: 4. 
     
     
         31 . The method of  claim 30 , wherein the IL-22 is in the form of an IL-22 dimer. 
     
     
         32 . The method of  claim 18 , wherein the IL-22 amino acid sequence is SEQ ID NO: 5. 
     
     
         33 . The method of  claim 32 , wherein the IL-22 is in the form of an IL-22 dimer. 
     
     
         34 . The method of  claim 27 , further comprising co-administering an immunosuppressive agent to the subject. 
     
     
         35 . The method of  claim 27 , further comprising co-administering prednisone to the subject.