Methods of Modulating Cytokine Activity; Related Reagents

Abstract

Provided are methods of modulating cytokine activity, e.g., for the purpose of treating immune and inflammatory disorders, including tumors and cancer. Also provided are methods of administering agonists or antagonists of IL-33 and IL-33 receptor.

1 . A method of modulating an immune disorder or condition, comprising administering an effective amount of an agonist or antagonist of IL-33 of IL-33 Receptor complex (IL-33R). 
     
     
         2 . The method of  claim 1 , wherein the disorder or condition comprises:
 a) innate response;   b) asthma or allergy;   c) multiple sclerosis;   d) an inflammatory bowel disorder;   e) arthritis;   f) infection;   g) a cancer or tumor.   
     
     
         3 . The method of  claim 2 , wherein the infection comprises:
 a) an intracellular pathogen;   b) a bacterium;   c) a parasite; or   d) a virus.   
     
     
         4 . The method of  claim 3 , wherein the intracellular pathogen is:
 a)  Leishmania  sp.;   b)  Mycobacterium  sp.;   c)  Listeria  sp.;   d)  Toxoplasma  sp.;   e)  Schistosoma ; or   f) a respiratory virus;   
     
     
         5 . The method of  claim 1 , wherein the immune disorder or conditions comprises:
 a) TH1-type response; or   b) TH2-type response.   
     
     
         6 . The method of  claim 5 , wherein the TH2-type response comprises an early event in TH2-type response. 
     
     
         7 . The method of  claim 1 , wherein the arthritis comprises:
 a) rheumatoid arthritis;   b) osteoarthritis; or   c) psoriatic arthritis.   
     
     
         8 . The method of  claim 1 , wherein the agonist comprises:
 a) IL-33 or;   b) a nucleic acid.   
     
     
         9 . The method of  claim 8 , wherein the nucleic acid encodes IL-33. 
     
     
         10 . The method of  claim 1 , wherein the antagonist comprises a binding composition from an antibody that specifically binds:
 a) IL-33;   b) an IL-33R complex; or   c) a complex of IL-33 and IL-33R.   
     
     
         11 . The method of  claim 10 , wherein the binding composition from an antibody comprises:
 a) a polyclonal antibody;   b) a monoclonal antibody;   c) a humanized antibody, or a fragment thereof,   d) an Fab, Fv, or F(ab′) 2  fragment;   e) a peptide mimetic of an antibody; or   f) a detectable label.   
     
     
         12 . The method of  claim 1 , wherein the antagonist comprises:
 a) a soluble IL-33R;   b) a small molecule; or   c) a nucleic acid.   
     
     
         13 . The method of  claim 12 , wherein the nucleic acid specifically hybridizes with a polynucleotide encoding IL-33. 
     
     
         14 . The method of  claim 13 , wherein the nucleic acid comprises:
 a) anti-sense nucleic acid; or   b) small interference RNA (siRNA).   
     
     
         15 . A method of modulating blood cell counts comprising administering an effective amount of an agonist or antagonist of IL-33. 
     
     
         16 . The method of  claim 15 , wherein the IL-33 agonist increases the counts of:
 a) total white blood cells;   b) neutrophils;   c) lymphocytes; or   d) eosinophils.   
     
     
         17 . The method of  claim 15 , wherein the IL-33 antagonist increases the count of platelets. 
     
     
         18 . The method of  claim 16 , wherein the IL-33 antagonist decreases the counts of:
 a) total white blood cells;   b) neutrophils;   c) lymphocytes; or   d) eosinophils.   
     
     
         19 . A method of diagnosing the immune condition or disorder of  claim 1 , comprising contacting a binding composition to a biological sample, wherein the binding composition specifically binds to IL-33, and measuring or determining the specific binding of the binding composition to the biological sample. 
     
     
         20 . A kit for the diagnosis of the immune condition or disorder of  claim 1 , comprising a compartment and a binding composition that specifically binds to:
 a) IL-33;   b) an IL-33R complex;   c) a complex of IL-33 and IL-33R; or   d) or a nucleic acid encoding IL-33.