METHODS OF MODULATING A MAMMALIAN CYTOKINE
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 - 20 . (canceled)
21 . A method of modulating an immune disorder or condition, comprising administering an effective amount of an antagonist of mature human IL-33, wherein the mature human IL-33 comprises residues 112-270 of SEQ ID NO:2.
22 . The method of claim 21 , wherein the immune disorder or condition comprises a TH2-type response.
23 . The method of claim 22 , wherein the TH2-type response comprises an early event in TH2-type response.
24 . The method of claim 21 , wherein the disorder or condition comprises asthma or allergy involving a pathogenic TH2-type response.
25 . The method of claim 21 , wherein the disorder or condition comprises:
a. multiple sclerosis;
b. an inflammatory bowel disorder; or
c. arthritis.
26 . The method of claim 21 , wherein the antagonist comprises a binding composition from an antibody that specifically binds to mature human IL-33.
27 . The method of claim 26 , wherein the binding composition from an antibody comprises a monoclonal antibody, or a fragment thereof.
28 . The method of claim 26 , wherein the binding composition from an antibody comprises a humanized antibody, or a fragment thereof.
29 . The method of claim 26 , wherein the binding composition from an antibody comprises an Fab, Fv, or F(ab′) 2 fragment.
30 . The method of claim 21 , wherein the antagonist is an antagonist comprising a soluble T1/ST2.
31 . The method of claim 29 , wherein the soluble T1/ST2 comprises residues 1-337 of SEQ ID NO: 6.
32 . The method of claim 21 , wherein the antagonist comprises:
a. anti-sense nucleic acid; or
b. small interference RNA (siRNA).
33 . A method of modulating an immune disorder or condition, comprising administering an effective amount of an agonist of mature human IL-33.
34 . The method of claim 32 , wherein the agonist is an agonist antibody, or antigen binding fragment thereof, that specifically binds to T1/ST2.
35 . The method of claim 32 , wherein the agonist comprises:
a. mature human IL-33; or
b. a nucleic acid encoding mature human IL-33.
36 . The method of claim 32 , wherein the immune disorder or condition comprises a TH1-type response.
37 . The method of claim 32 , wherein the immune disorder or condition comprises:
a. innate response;
b. infection; or
c. a cancer or tumor.
38 . A method of modulating blood cell counts comprising administering an effective amount of an agonist or antagonist of mature human IL-33.
39 . A method of diagnosing an immune condition or disorder, comprising:
a. contacting a binding composition to a biological sample, wherein the binding composition specifically binds to mature human IL-33; and
b. measuring or determining the specific binding of the binding composition to the biological sample.
40 . A kit for the diagnosis of an immune condition or disorder, comprising:
a. a compartment; and
b. a binding composition that specifically binds to:
i) mature human IL-33;
ii) a nucleic acid encoding mature human IL-33; or
iii) T1/ST2.