Uses of Mammalian Cytokine; Related Reagents

Abstract

Provided are methods of treatment for inflammatory and autoimmune disorders of the metabolic system. Also provided are methods of diagnosis.

1 . A method of treating an individual predisposed to develop an IL-23 mediated autoimmune disorder of the metabolic system comprising administering an effective amount of an antagonist of IL-23 or IL-23 Receptor (IL-23R). 
     
     
         2 . The method of  claim 1 , wherein the disorder of the metabolic system is diabetes mellitus. 
     
     
         3 . The method of  claim 1 , wherein the antagonist specifically binds to a polypeptide or nucleic acid of:
 a) IL-23p19; or   b) IL-23R.   
     
     
         4 . The method of  claim 1 , wherein the antagonist comprises a:
 a) nucleic acid; or   b) small molecule.   
     
     
         5 . The method of  claim 4 , wherein the nucleic acid comprises:
 a) anti-sense nucleic acid; or   b) small interfering RNA (siRNA).   
     
     
         6 . The method of  claim 1 , wherein the antagonist comprises:
 a) an antigen binding fragment of an antibody; or   b) a soluble receptor derived from IL-23R.   
     
     
         7 . The method of  claim 6 , wherein the antibody is:
 a) a polyclonal antibody;   b) a monoclonal antibody;   c) a humanized antibody;   d) an Fab, Fv, or F(ab′) 2  fragment;   e) a single chain antibody;   f) a peptide mimetic of an antibody; or   g) detectably labeled.   
     
     
         8 . The method of  claim 1 , wherein the antagonist of IL-23 is co-administered with an:
 a) IL-12 antagonist;   b) TNFα antagonist;   c) IL-6 antagonist;   d) IL-17 antagonist; or   e) IL-10 agonist.   
     
     
         9 . The method of  claim 1 , wherein the antagonist of IL-23 is co-administered with an immunosuppressive agent. 
     
     
         10 . The method of  claim 1 , wherein the immunosuppressive agent is:
 a) prednisone;   b) azathioprine; or   c) cyclosporin.   
     
     
         11 . A method of treating an individual exhibiting signs of impaired glucose homeostasis to prevent development of diabetes mellitus, the method comprising administering to the individual an effective amount of an antagonist of IL-23 or IL-23R. 
     
     
         12 . The method of  claim 11 , wherein impaired glucose homeostasis is measured by plasma glucose levels either during fasting or after a glucose load. 
     
     
         13 . The method of  claim 12 , wherein the plasma glucose levels are:
 a) between 110 to 126 mg per dL during fasting; or   b) between 140 and 200 mg per dL after a glucose load.   
     
     
         14 . The method of  claim 11 , wherein the antagonist of IL-23 or IL-23R is an antibody or an antigen binding fragment thereof. 
     
     
         15 . The method of  claim 14 , wherein the antibody or antigen binding fragment thereof is:
 a) a polyclonal antibody;   b) a monoclonal antibody;   c) a humanized antibody;   d) an Fab, Fv, or F(ab′) 2  fragment;   e) a single chain antibody   f) a peptide mimetic of an antibody; or   g) detectably labeled.   
     
     
         16 . The method of  claim 15 , wherein the antibody or antigen binding fragment thereof is co-administered with an immunosuppressive agent. 
     
     
         17 . The method of  claim 16 , wherein the immunosuppressive agent is:
 a) prednisone;   b) azathioprine; or   c) cyclosporin.