Soluble zcytor 11 cytokine receptors

Abstract

Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for soluble zcytor11 receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides and antibodies can also be used to block TIF activity in vitro and in vivo, and may be used in conjunction with TIF and other cytokines to selectively stimulate the immune system. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

1 . A method of reducing IL-TIF-induced inflammation or suppressing an IL-TIF-induced inflammatory response comprising administering to a mammal with inflammation an amount of a composition of soluble cytokine receptor comprising SEQ ID NO:3 sufficient to reduce inflammation or suppress the inflammatory response.  
     
     
         2 . A method of suppressing an IL-TIF-induced inflammatory response in a mammal exposed to an antigen or pathogen comprising: 
 (1) determining a level of an antigen- or pathogen-specific antibody;    (2) administering a composition comprising a soluble cytokine receptor polypeptide comprising SEQ ID NO:3 in an acceptable pharmaceutical vehicle;    (3) determining a post administration level of antigen- or pathogen-specific antibody;    (4) comparing the level of antibody in step (1) to the level of antibody in step (3), wherein a lack of increase or a decrease in antibody level is indicative of suppressing the immune response.    
     
     
         3 . The method of  claim 1 , wherein the soluble cytokine receptor further comprises a soluble CRF2-4 polypeptide (SEQ ID NO:33)  
     
     
         4 . The method of  claim 2 , wherein the soluble cytokine receptor further comprises a soluble CRF2-4 polypeptide (SEQ ID NO:33).  
     
     
         5 . A method of suppressing an IL-TIF-induced inflammatory response in a mammal with inflammation comprising: 
 (1) determining a level of SAA protein;    (2) administering a composition comprising a soluble cytokine receptor polypeptide comprising SEQ ID NO:3 in an acceptable pharmaceutical vehicle;    (3) determining a post administration level of SAA protein;    (4) comparing the level of SAA protein in step (1) to the level of SAA protein in step (3), wherein a lack of increase or a decrease in SAA protein level is indicative of suppressing the inflammatory response.    
     
     
         6 . The method of  claim 5 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag, label, chemical moiety, toxin, biotin/avidin label, radionuclide, enzyme, substrate, cofactor, inhibitor, fluorescent marker, chemiluminescent marker, cytotoxic molecule or an immunoglobulin Fc domain.  
     
     
         7 . The method of  claim 5 , wherein the soluble cytokine receptor further comprises a soluble CRF2-4 polypeptide (SEQ ID NO:33).  
     
     
         8 . A method of treating a mammal afflicted with an IL-TIF-induced inflammatory disease in which IL-TIF plays a role, comprising: 
 administering an antagonist of IL-TIF to the mammal such that the inflammation is reduced, wherein the antagonist comprises a polypeptide or cytokine-binding polypeptide fragment of SEQ ID NO:3; and    wherein the inflammatory activity of IL-TIF is reduced.    
     
     
         9 . The method of  claim 8 , wherein the disease is a chronic inflammatory disease.  
     
     
         10 . The method of  claim 9 , wherein the disease is a chronic inflammatory disease selected from the group consisting of: 
 (a) inflammatory bowel disease;    (b) colitis;    (c) Crohn's disease;    (d) arthritis;    (e) asthma; and    (f) psoriasis.    
     
     
         11 . The method of  claim 8 , wherein the disease is an acute inflammatory disease.  
     
     
         12 . The method of  claim 11 , wherein the disease is an acute inflammatory disease selected from the group consisting of: 
 (a) sepsis;    (b) allergy; and    (c) infectious disease.    
     
     
         13 . The method of  claim 8 , wherein the polypeptide or cytokine-binding polypeptide fragment further comprises an affinity tag, label, chemical moiety, toxin, biotin/avidin label, radionuclide, enzyme, substrate, cofactor, inhibitor, fluorescent marker, chemiluminescent marker, cytotoxic molecule or an immunoglobulin Fc domain.  
     
     
         14 . The method of  claim 8 , wherein the antagonist further comprises a polypeptide or cytokine-binding polypeptide fragment of soluble CRF2-4 (SEQ ID NO:33).  
     
     
         15 . An isolated soluble cytokine receptor polypeptide complex comprising more than one soluble receptor subunit, wherein at least one of the soluble receptor subunits comprises a sequence of amino acid residues shown in SEQ ID NO:3, and 
 wherein a second soluble receptor subunits comprises a soluble Class I or Class II cytokine receptor, and    wherein the soluble cytokine receptor polypeptide binds IL-TIF or antagonizes IL-TIF activity.    
     
     
         16 . An isolated polypeptide according to  claim 15 , wherein the soluble cytokine receptor polypeptide comprises a heterodimeric receptor or homodimeric receptor complex.  
     
     
         17 . An isolated polypeptide according to  claim 15 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag, label, chemical moiety, toxin, biotin/avidin label, radionuclide, enzyme, substrate, cofactor, inhibitor, fluorescent marker, chemilurninescent marker, cytotoxic molecule or an immunoglobulin Fc domain.  
     
     
         18 . An isolated soluble cytokine receptor polypeptide complex consisting of two soluble receptor subunits, wherein at least one of the soluble receptor subunits consists of a sequence of amino acid residues shown in SEQ ID NO:3, and 
 wherein a second soluble receptor subunit consists of a soluble Class I or Class II cytokine receptor; and    wherein the soluble cytokine receptor polypeptide binds IL-TIF or antagonizes IL-TIF activity.    
     
     
         19 . An isolated polypeptide according to  claim 18 , wherein the soluble cytokine receptor polypeptide comprises a heterodimeric receptor or homodimeric receptor complex.  
     
     
         20 . An isolated polypeptide according to  claim 18 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag, label, chemical moiety, toxin, biotin/avidin label, radionuclide, enzyme, substrate, cofactor, inhibitor, fluorescent marker, chemiluminescent marker, cytotoxic molecule or an immunoglobulin Fc domain.  
     
     
         21 . The isolated polypeptide according to  claim 15 , wherein the soluble cytokine receptor polypeptide comprises a multimeric receptor complex.  
     
     
         22 . An isolated soluble cytokine receptor polypeptide complex comprising more than one soluble receptor subunit, wherein at least one of the soluble receptor subunits comprises a sequence of amino acid residues shown in SEQ ID NO:3, and 
 wherein a second soluble receptor subunit comprises a soluble CRF2-4 polypeptide (SEQ ID NO:33).    
     
     
         23 . An isolated soluble cytokine receptor polypeptide complex consisting of two soluble receptor subunits, wherein at least one of the soluble receptor subunits consists of a sequence of amino acid residues shown in SEQ ID NO:3, and 
 wherein a second soluble receptor subunit consists of soluble CRF2-4 polypeptide (SEQ ID NO:33).    
     
     
         24 . An isolated polypeptide according to  claim 22 , wherein the soluble cytokine receptor polypeptide comprises a heterodimeric receptor complex.  
     
     
         25 . The isolated polypeptide according to  claim 22 , wherein the soluble cytokine receptor polypeptide comprises a multimeric receptor complex.  
     
     
         26 . An isolated polypeptide according to  claim 22 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag, label, chemical moiety, toxin, biotin/avidin label, radionuclide, enzyme, substrate, cofactor, inhibitor, fluorescent marker, chemiluminescent marker, cytotoxic molecule or an immunoglobulin Fc domain.  
     
     
         27 . An isolated polypeptide according to  claim 23 , wherein the soluble cytokine receptor polypeptide comprises a heterodimeric receptor receptor complex.  
     
     
         28 . An isolated polypeptide according to  claim 23 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag, label, chemical moiety, toxin, biotin/avidin label, radionuclide, enzyme, substrate, cofactor, inhibitor, fluorescent marker, chemiluminescent marker, cytotoxic molecule or an immunoglobulin Fc domain.  
     
     
         29 . A method for inhibiting IL-TIF-induced proliferation of neutrophils or platelets comprising culturing bone marrow or peripheral blood cells with a composition comprising an amount of soluble cytokine receptor comprising SEQ ID NO:3 and a soluble A soluble IL-10 receptor polypeptide (SEQ ID NO:34) sufficient to reduce proliferation of the neutrophils or platelets in the bone marrow or peripheral blood cells as compared to bone marrow or peripheral blood cells cultured in the absence of the soluble cytokine receptor.  
     
     
         30 . An isolated soluble cytokine receptor polypeptide complex comprising more than one soluble receptor subunit, wherein at least one of the soluble receptor subunits comprises the sequence of amino acid residues shown in SEQ ID NO:3, and 
 wherein a second soluble receptor subunit comprises the soluble A soluble IL-receptor polypeptide (SEQ ID NO:34), and    wherein the soluble cytokine receptor polypeptide binds IL-TIF or antagonizes IL-TIF activity.    
     
     
         31 . An isolated soluble cytokine receptor polypeptide complex consisting of two soluble receptor subunits, wherein at least one of the soluble receptor subunits consists of the sequence of amino acid residues shown in SEQ ID NO:3, and 
 wherein a second soluble receptor subunit consists of soluble A soluble IL-10 receptor polypeptide (SEQ ID NO:34), and    wherein the soluble cytokine receptor polypeptide binds EL-TIF or antagonizes IL-TIF activity.    
     
     
         32 . An isolated polypeptide according to  claim 30 , wherein the soluble cytokine receptor polypeptide comprises a heterodimeric receptor complex.  
     
     
         33 . The isolated polypeptide according to  claim 30 , wherein the soluble cytokine receptor polypeptide comprises a multimeric receptor complex.  
     
     
         34 . An isolated polypeptide according to  claim 30 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag, label, chemical moiety, toxin, biotin/avidin label, radionuclide, enzyme, substrate, cofactor, inhibitor, fluorescent marker, chemiluminescent marker, cytotoxic molecule or an immunoglobulin Fc domain.  
     
     
         35 . An isolated polypeptide according to  claim 31 , wherein the soluble cytokine receptor polypeptide comprises a heterodimeric receptor receptor complex.  
     
     
         36 . An isolated polypeptide according to  claim 31 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag, label, chemical moiety, toxin, biotin/avidin label, radionuclide, enzyme, substrate, cofactor, inhibitor, fluorescent marker, chemiluminescent marker, cytotoxic molecule or an immunoglobulin Fc domain.