USES OF MAMMALIAN CYTOKINE; RELATED REAGENTS
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.