Uses of mammalian cytokine; related reagents

Abstract

Provided are cytokines and methods of modulating activity of the immune system using cytokine agonists and antagonists. Also provided are methods of treatment of immune and proliferative disorders.

1 . A method of modulating interferon-gamma (IFNgamma) production by a cell, comprising treating the cell with an effective amount of an agonist or antagonist of the cytokine IL-27. 
     
     
         2 . The method of  claim 1 , wherein the modulating is:
 a) increasing and the treating is with an agonist of IL-27; or   b) decreasing and the treating is with an antagonist of IL-27.   
     
     
         3 . The method of  claim 1 , wherein the agonist is an IL-27 variant or derivative, and the IL-27 variant or derivative possesses at least one IL-27 biological property. 
     
     
         4 . The method of  claim 3 , wherein the IL-27 variant or derivative comprises an IL-27 hyperkine. 
     
     
         5 . The method of  claim 2 , wherein the increasing is about two-fold, about 5-fold, about 10-fold, about 20-fold, or about 50-fold greater than the expression or production level in the absence of the effective amount of IL-27, or an IL-27 variant or derivative. 
     
     
         6 . The method of  claim 2 , wherein:
 a) the treating with an agonist further comprises treating with an agonist of IL-12 and an agonist of an additional cytokine; or   b) the treating with an antagonist further comprises treating with an antagonist of IL-12 and an antagonist of an additional cytokine.   
     
     
         7 . The method of  claim 6 , wherein the additional cytokine is:
 a) IL-2;   b) IL-15;   c) IL-23; or   d) IL-18.   
     
     
         8 . The method of  claim 2 , wherein:
 a) the treating with an agonist further comprises treating with an agonist of two additional cytokines; or   b) the treating with an antagonist further comprises treating with an antagonist of two additional cytokines.   
     
     
         9 . The method of  claim 8 , wherein the two additional cytokines are:
 a) IL-2 and IL-15;   b) IL-2 and IL-23;   c) IL-15 and IL-23; or   d) IL-18 and IL-2, IL-15, or IL-23.   
     
     
         10 . The method of  claim 2 , wherein:
 a) the agonist treated cell is treated with agonists of three additional cytokines; or   b) the antagonist treated cell is treated with antagonists of three additional cytokines.   
     
     
         11 . The method of  claim 10 , wherein the three additional cytokines are IL-18 and:
 a) IL-2 and IL-15; and   b) IL-12 and IL-23.   
     
     
         12 . The method of  claim 1 , wherein the cell is a:
 a) T cell; or   b) NK cell.   
     
     
         13 . The method of  claim 2 , wherein the cell is located in a subject, and the IL-27 agonist or IL-27 antagonist is administered to the subject. 
     
     
         14 . The method of  claim 13 , wherein the subject has, or is suspected of having, a disorder or pathological condition that can be treated or ameliorated by modulating IFNgamma levels in the subject. 
     
     
         15 . The method of  claim 14 , wherein the treating is with an agonist or antagonist of IL-27 and the disorder or condition comprises:
 a) cancer, neoplasm, or tumor;   b) an intracellular pathogen; or   c) an inflammatory or autoimmune condition.   
     
     
         16 . The method of  claim 15 , wherein the treating is with an agonist of IL-27 and the intracellular pathogen comprises:
 a)  Leishmania  sp.;   b)  Mycobacterium  sp.;   c)  Listeria  sp.;   d)  Toxoplasma  sp.;   e) herpesvirus;   f) cytomegalovirus; or   g) human immunodeficiency virus (HIV).   
     
     
         17 . The method of  claim 15 , wherein the treating is with an agonist of IL-27 and the inflammatory or autoimmune condition comprises:
 a) rheumatoid arthritis; or   b) asthma or allergy.   
     
     
         18 . The method of  claim 15 , wherein the treating is with an antagonist if IL-27 and the disorder or condition comprises:
 a) a TH1 condition or disorder;   b) multiple sclerosis;   c) psoriasis;   d) Crohn's disease;   e) type I diabetes; or   f) systemic lupus erythematosus.   
     
     
         19 . A method of treating or ameliorating a disorder or pathological condition of a subject by modulating production of IFNgamma in the subject, comprising administering an effective amount of an agonist or antagonist of the cytokine IL-27. 
     
     
         20 . The method of  claim 19 , wherein the subject is a:
 a) human subject; or   b) veterinary subject.   
     
     
         21 . The method of  claim 19 , wherein the modulating is:
 a) increasing and the treating is with an agonist of IL-27; or   b) decreasing and the treating is with an antagonist of IL-27.   
     
     
         22 . The method of  claim 19 , wherein the agonist is an IL-27 variant or derivative, and the IL-27 variant or derivative possesses at least one IL-27 biological property. 
     
     
         23 . The method of  claim 22 , wherein the IL-27 variant or derivative comprises an IL-27 hyperkine. 
     
     
         24 . The method of  claim 21 , wherein the increasing is about two-fold, about 5-fold, about 10-fold, about 20-fold, or about 50-fold greater than the expression or production level in the absence of the administered effective amount of the IL-27, or an IL-27 variant or derivative. 
     
     
         25 . The method of  claim 19 , wherein:
 a) the agonist treated subject is treated with an agonist of IL-12 and an agonist of one additional cytokine; or   b) the antagonist treated subject is treated with an antagonist of IL-12 and an antagonist of one additional cytokine.   
     
     
         26 . The method of  claim 25 , wherein the additional cytokine is:
 a) IL-2;   b) IL-15;   c) IL-23; or   d) IL-18.   
     
     
         27 . The method of  claim 19 , wherein:
 a) the agonist treated subject is treated with agonists of two additional cytokines; or   b) the antagonist treated subject is treated with antagonists of two additional cytokines.   
     
     
         28 . The method of  claim 27 , wherein the two additional cytokines are:
 a) IL-2 and IL-15;   b) IL-2 and IL-23;   c) IL-15 and IL-23; or   d) IL-18 and IL-2, IL-15, or IL-23.   
     
     
         29 . The method of  claim 19 , wherein:
 a) the agonist treated subject is treated with agonists of three additional cytokines; or   b) the antagonist treated subject is treated with antagonists of three additional cytokines.   
     
     
         30 . The method of  claim 29 , wherein the three additional cytokines are IL-18 and:
 a) IL-2 or IL-15; and   b) IL-12 or IL-23.   
     
     
         31 . The method of  claim 19 , wherein the subject has, or is suspected of having, a disorder or condition that can be treated or ameliorated by modulating levels of IFNgamma in the subject. 
     
     
         32 . The method of  claim 19 , wherein the treating is with an agonist or antagonist of IL-27 and the disorder or condition comprises:
 a) cancer, neoplasm, or tumor;   b) an intracellular pathogen; or   c) an inflammatory or autoimmune condition.   
     
     
         33 . The method of  claim 32 , wherein the treating is with an agonist of IL-27 and the intracellular pathogen comprises:
 a)  Leishmania  sp.;   b)  Mycobacterium  sp.;   c)  Listeria  sp.;   d)  Toxoplasma  sp.;   e) herpesvirus;   f) cytomegalovirus; or   g) human immunodeficiency virus (HIV).   
     
     
         34 . The method of  claim 32 , wherein the treating is with an agonist of IL-27 and the inflammatory or autoimmune condition comprises:
 a) rheumatoid arthritis; or   b) asthma or allergy.   
     
     
         35 . The method of  claim 32 , wherein the treating is with an antagonist of IL-27 and the inflammatory or autoimmune condition comprises:
 a) a TH1 condition or disorder;   b) multiple sclerosis;   c) psoriasis;   d) Crohn's disease;   e) type I diabetes; or   f) systemic lupus erythematosus.   
     
     
         36 . The method of  claim 19 , wherein the antagonist is:
 a) derived from the antigen binding site of an antibody; or   b) a nucleic acid.