Il-1 family variants

Abstract

The present invention provides compositions and methods relating to IL-1Rrp2 requiring proteins.

What is claimed is: 
     
         1 . An isolated IL-1F5 polypeptide that antagonizes signal transduction/activation through IL-1Rrp2, the IL-1F5 polypeptide comprising an amino acid sequence having a methionine at position ten of the amino acid sequence, position ten being relative to the N-terminal amino acid at position one of the amino acid sequence. 
     
     
         2 . The isolated IL-1F5 polypeptide of  claim 1 , wherein the N-terminal amino acid at position one is valine. 
     
     
         3 . The isolated IL-1F5 polypeptide of  claim 1 , wherein the N-terminal amino acid at position one is a methionine. 
     
     
         4 . The isolated IL-1F5 polypeptide of  claim 1 , wherein the amino acid at position two relative to the N-terminal amino acid at position one, is a leucine. 
     
     
         5 . The isolated IL-1F5 polypeptide of  claim 1 , wherein the isolated IL-1F5 polypeptide antagonizes signal transduction/activation through IL-1Rrp2 more than an IL-1F5 polypeptide consisting of SEQ ID NO 1. 
     
     
         6 . The isolated IL-1F5 polypeptide of  claim 1  comprising an amino acid sequence selected from the group consisting of: SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8 and SEQ ID NO 9. 
     
     
         7 . A nucleic acid sequence encoding the IL-1F5 polypeptide of  claim 1 . 
     
     
         8 . A recombinant vector that directs expression of the nucleic acid of  claim 7 . 
     
     
         9 . A host cell transfected or transduced with the vector of  claim 8 . 
     
     
         10 . A method of producing an IL-1F5 polypeptide comprising culturing the host cell of  claim 9  under conditions promoting expression and isolating the expressed IL-1F5 polypeptide. 
     
     
         11 . A composition comprising the polypeptide of  claim 1  and a physiologically acceptable diluent, excipient or carrier. 
     
     
         12 . A method of treating an inflammatory or autoimmune condition in a subject wherein the inflammatory or autoimmune condition is mediated by IL-1Rrp2, comprising administering to the subject in an amount of the IL-1F5 polypeptide of  claim 1  sufficient to reduce at least one symptom of the inflammatory or autoimmune condition in the subject. 
     
     
         13 . The method of  claim 12 , wherein the condition to be treated is an inflammatory condition of the skin, lungs or airways mediated by IL-1Rrp2. 
     
     
         14 . The method of  claim 12 , wherein the condition to be treated is selected from the group consisting of psoriasis, seborrheic dermatitis, atopic dermatitis, including chronic atopic dermatitis, allergic contact dermatitis, lichen simplex chronicus,  pityriasis rubra  pilaris, nummular dermatitis, asthma, allergic rhinitis, gastro-esophageal reflux disease, arthritic conditions including, rheumatoid arthritis, psoriatic arthritis, and osteoarthritis. 
     
     
         15 . The method of  claim 12 , wherein the subject is human. 
     
     
         16 . An isolated IL-1F6 polypeptide that agonizes signal transduction/activation through IL-1Rrp2, wherein the IL-1F6 polypeptide comprises an amino acid sequence having a isoleucine at position ten of the amino acid sequence, position ten being relative to the N-terminal amino acid at position one of the amino acid sequence. 
     
     
         17 . The isolated IL-1F6 polypeptide of  claim 16 , wherein the N-terminal amino acid at position one is a lysine. 
     
     
         18 . The isolated IL-1F6 polypeptide of  claim 16 , wherein the N-terminal amino acid at position one is a methionine. 
     
     
         19 . The isolated IL-1F6 polypeptide of  claim 16 , wherein the amino acid at position two relative to the N-terminal amino acid at position one of the amino acid sequence, is an isoleucine. 
     
     
         20 . The isolated IL-1F6 polypeptide of  claim 16 , wherein the isolated IL-1F6 polypeptide agonizes signal transduction/activation through IL-1Rrp2 more than an IL-1F6 polypeptide consisting of SEQ ID NO 2. 
     
     
         21 . The isolated IL-1F6 polypeptide of  claim 16 , comprising an amino acid sequence selected from the group consisting of: SEQ ID NO 10, SEQ ID NO 11, SEQ ID NO 12, SEQ ID NO 13, SEQ ID NO 65, SEQ ID NO 66, SEQ ID NO 67 and SEQ ID NO 68. 
     
     
         22 . A nucleic acid sequence encoding the IL-1F6 of  claim 16 . 
     
     
         23 . A recombinant vector that directs expression of the nucleic acid of  claim 22 . 
     
     
         24 . A host cell transfected or transduced with the vector of  claim 23 . 
     
     
         25 . A method of producing an IL-1F6 polypeptide comprising culturing the host cell of  claim 24  under conditions promoting expression and isolating the expressed IL-1F6 polypeptide. 
     
     
         26 . A composition comprising the polypeptide of  claim 16  and a physiologically acceptable diluent, excipient or carrier. 
     
     
         27 . A method of stimulating the immune system of an immunosuppresed patient, comprising administering the IL-1F6 polypeptide according to  claim 16  to an immunosuppresed patient in an amount sufficient to stimulate the patient's immune system. 
     
     
         28 . An antibody that specifically binds an IL-1F6 polypeptide and prevents proteolytic cleavage thereof. 
     
     
         29 . The antibody of  claim 28 , wherein the antibody is a monoclonal antibody. 
     
     
         30 . A composition comprising the antibody of  claim 28  and a physiologically acceptable diluent, excipient or carrier. 
     
     
         31 . A method of treating an inflammatory or autoimmune condition mediated by IL-1Rrp2, comprising administering the IL-1F6 antibody of  claim 29  to a subject in an amount sufficient to ameliorate at least one symptom of the condition. 
     
     
         32 . The method of  claim 31 , wherein the condition to be treated is an inflammatory condition of the skin, lungs or airways mediated by IL-1Rrp2. 
     
     
         33 . The method of  claim 31 , wherein the condition to be treated is selected from the group consisting of psoriasis, seborrheic dermatitis, atopic dermatitis, including chronic atopic dermatitis, allergic contact dermatitis, lichen simplex chronicus,  pityriasis rubra  pilaris, nummular dermatitis, asthma, allergic rhinitis, gastro-esophageal reflux disease, arthritic conditions including, rheumatoid arthritis, psoriatic arthritis, and osteoarthritis. 
     
     
         34 . The method of  claim 31 , wherein the subject is human. 
     
     
         35 . An isolated IL-1F8 polypeptide that agonizes signal transduction/activation through IL-1Rrp2, wherein the IL-1F8 polypeptide comprises an amino acid sequence having a isoleucine at position ten of the amino acid sequence, position ten being relative to the N-terminal amino acid at position one of the amino acid sequence. 
     
     
         36 . The isolated IL-1F8 polypeptide of  claim 35 , wherein the N-terminal amino acid at position one is an arginine. 
     
     
         37 . The isolated IL-1F8 polypeptide of  claim 35 , wherein the N-terminal amino acid at position one is a methionine. 
     
     
         38 . The isolated IL-1F8 polypeptide of  claim 35 , wherein the amino acid at position two, position two being relative to the N-terminal amino acid at position one, is a glutamic acid. 
     
     
         39 . The isolated IL-1F8 polypeptide of  claim 35 , wherein the isolated IL-1F6 polypeptide agonizes signal transduction/activation through IL-1Rrp2 more than an IL-1F8 polypeptide consisting of SEQ ID NO 3. 
     
     
         40 . The isolated IL-1F8 polypeptide of  claim 35 , comprising an amino acid sequence selected from the group consisting of: SEQ ID NO 14, SEQ ID NO 15, SEQ ID NO 16 and SEQ ID NO 17. 
     
     
         41 . A nucleic acid sequence encoding the IL-1F8 polypeptide of  claim 35 . 
     
     
         42 . A recombinant vector that directs expression of the nucleic acid of  claim 41 . 
     
     
         43 . A host cell transfected or transduced with the vector of  claim 42 . 
     
     
         44 . A method of producing an IL-1F8 polypeptide comprising culturing the host cell of  claim 43  under conditions promoting expression and isolating the expressed IL-1F8 polypeptide. 
     
     
         45 . A composition comprising the polypeptide of  claim 35  and a physiologically acceptable diluent, excipient or carrier. 
     
     
         46 . A method of stimulating the immune system of an immunosuppresed patient, comprising administering the IL-1F8 polypeptide according to  claim 35  to an immunosuppresed patient in an amount sufficient to stimulate the patient's immune system. 
     
     
         47 . An antibody that specifically binds an IL-1F8 polypeptide and prevents proteolytic cleavage thereof. 
     
     
         48 . The antibody of  claim 47 , wherein the antibody is a monoclonal antibody. 
     
     
         49 . A composition comprising the antibody of  claim 47  and a physiologically acceptable diluent, excipient or carrier. 
     
     
         50 . A method of treating an inflammatory or autoimmune condition mediated by IL-1Rrp2, comprising administering the IL-1F8 antibody of  claim 47  to a subject in and amount sufficient to ameliorate at least one symptom. 
     
     
         51 . The method of  claim 50 , wherein the condition to be treated is an inflammatory condition of the skin, lungs or airways mediated by IL-1Rrp2. 
     
     
         52 . The method of  claim 50 , wherein the condition to be treated is selected from the group consisting of psoriasis, seborrheic dermatitis, atopic dermatitis, including chronic atopic dermatitis, allergic contact dermatitis, lichen simplex chronicus,  pityriasis rubra  pilaris, nummular dermatitis, asthma, allergic rhinitis, gastro-esophageal reflux disease, arthritic conditions including, rheumatoid arthritis, psoriatic arthritis, and osteoarthritis. 
     
     
         53 . An isolated IL-1F9 polypeptide that agonizes signal transduction/activation through IL-1Rrp2, wherein the IL-1F9 polypeptide comprises an amino acid sequence having a isoleucine at position ten of the amino acid sequence, position ten being relative to the N-terminal amino acid at position one of the amino acid sequence. 
     
     
         54 . The isolated IL-1F9 polypeptide of  claim 53 , wherein the N-terminal amino acid at position one is a serine. 
     
     
         55 . The isolated IL-1F9 polypeptide of  claim 53 , wherein the N-terminal amino acid at position one is a methionine. 
     
     
         56 . The isolated IL-1F9 polypeptide of  claim 53 , wherein the amino acid at position two relative to the N terminal amino acid at position one, is a methionine. 
     
     
         57 . The isolated IL-1F9 polypeptide of  claim 53 , wherein the isolated IL-1F9 polypeptide agonizes signal transduction/activation through IL-1Rrp2 more than an IL-1F9 polypeptide having an amino acid sequence consisting of SEQ ID NO 4. 
     
     
         58 . The isolated IL-1F9 polypeptide of  claim 53 , comprising an amino acid sequence selected from the group consisting of: SEQ ID NO 18, SEQ ID NO 19, SEQ ID NO 20 and SEQ ID NO 21. 
     
     
         59 . A nucleic acid sequence encoding the IL-1F9 polypeptide of  claim 53 . 
     
     
         60 . A recombinant vector that directs expression of the nucleic acid of  claim 59 . 
     
     
         61 . A host cell transfected or transduced with the vector of  claim 60 . 
     
     
         62 . A method of producing an IL-1F9 polypeptide comprising culturing the host cell of  claim 52  under conditions promoting expression and isolating the expressed IL-1F9 polypeptide. 
     
     
         63 . A composition comprising the polypeptide of  claim 53  and a physiologically acceptable diluent, excipient or carrier. 
     
     
         64 . A method of stimulating the immune system of an immunosuppresed patient, comprising administering the IL-1F9 polypeptide according to  claim 53  to an immunosuppresed patient in an amount sufficient to stimulate the patient's immune system. 
     
     
         65 . An antibody that specifically binds an IL-1F9 polypeptide and prevents proteolytic cleavage thereof. 
     
     
         66 . The antibody of  claim 65 , wherein the antibody is a monoclonal antibody. 
     
     
         67 . A composition comprising the antibody of  claim 65  and a physiologically acceptable diluent, excipient or carrier. 
     
     
         68 . A method of treating an inflammatory or autoimmune condition mediated by IL-1Rrp2, comprising administering the IL-1F9 antibody of  claim 65  to a subject in an amount sufficient to ameliorate at least one symptom of the condition. 
     
     
         69 . The method of  claim 68 , wherein the condition to be treated is an inflammatory condition of the skin, lungs or airways mediated by IL-1Rrp2. 
     
     
         70 . The method of  claim 68 , wherein the condition to be treated is selected from the group consisting of psoriasis, seborrheic dermatitis, atopic dermatitis, including chronic atopic dermatitis, allergic contact dermatitis, lichen simplex chronicus,  pityriasis rubra  pilaris, nummular dermatitis, asthma, allergic rhinitis, gastro-esophageal reflux disease, arthritic conditions including, rheumatoid arthritis, psoriatic arthritis, and osteoarthritis. 
     
     
         71 . The method of  claim 68 , wherein the subject is human. 
     
     
         72 . A method of identifying a protease that cleaves an IL-1 family member comprising contacting a source of the protease with the IL-1 family member under conditions promoting proteolytic cleavage of the IL-1 family member, and determining if the IL-1 family member has been proteolytically cleaved. 
     
     
         73 . A method of identifying an inhibitor of a protease that cleaves an IL-1 family member comprising contacting the protease with the IL-1 family member in the presence, and absence, of a molecule that is a potential inhibitor, under conditions promoting proteolytic cleavage of the IL-1 family member, and determining if the IL-1 family member has been proteolytically cleaved, wherein if the IL-1 family member is not cleaved or is cleaved to a lesser degree in the presence of the molecule, the molecule is an inhibitor.