Interleukin-9 and Interleukin-4 Chimeric Antagonist Muteins and Methods of Using Same

Abstract

Chimeric polypeptide antagonists that include an interleukin-4 (IL-4) mutein linked to an interleukin-9 (IL-9) mutein are provided, as are polynucleotides encoding the IL-4 and IL-9 chimeric mutein antagonists. Also provided are methods of using the chimeric mutein antagonists and encoding polypeptides to reduce or inhibit the responsiveness of a cell to a cytokine such as IL-4, IL-9 and/or interleukin-13. Methods using the compositions to treat disorders such as pulmonary disorders (e.g., asthma) also are provided.

1 . A chimeric polypeptide, comprising an interleukin-4 (IL-4) mutein receptor antagonist operatively linked to an interleukin-9 (IL-9) mutein receptor antagonist, wherein the chimeric polypeptide can reduce or inhibit the association of an interleukin with an IL-4 receptor, an IL-9 receptor, an interleukin-13 (IL-13) receptor, or a combination thereof. 
     
     
         2 . A method of reducing or inhibiting cytokine responsiveness of a cell, comprising contacting the cell with a chimeric polypeptide of  claim 1 . 
     
     
         3 . The method of  claim 2 , wherein the cytokine responsiveness of the cell comprises proliferation of the cell, protein expression by the cell, or a combination thereof. 
     
     
         4 . The method of  claim 2 , wherein the cytokine responsiveness comprises IL-4 responsiveness, IL-9 responsiveness, IL-13 responsiveness, or a combination thereof. 
     
     
         5 . The method of  claim 2 , wherein cell comprises a lymphocyte, a polymorphonuclear leukocyte, a monocyte, or a combination thereof. 
     
     
         6 . The method of  claim 5 , wherein the cell comprises a B lymphocyte, a T lymphocyte, an eosinophil, or a combination thereof. 
     
     
         7 . The method of  claim 2 , wherein the cell comprises a leukemia cell. 
     
     
         8 . The method of  claim 7 , wherein the leukemia cell comprises an erythroleukemia cell or a megakaryoblastic leukemia cell. 
     
     
         9 . A method of ameliorating a pathologic condition associated with cells expressing at least one receptor selected from an IL-4 receptor, an IL-9 receptor, or an IL-13 receptor in a subject, comprising administering to the subject a chimeric polypeptide of  claim 1  in an amount sufficient to reduce or inhibit specific binding of IL-4, IL-9 IL-13, or a combination thereof to the receptor, thereby ameliorating the pathologic condition in the subject. 
     
     
         10 . The method of  claim 9 , wherein the subject is a mammal. 
     
     
         11 . The method of  claim 9 , wherein the subject is a human. 
     
     
         12 . The method of  claim 9 , wherein the pathologic condition comprises asthma, chronic obstructive pulmonary disease, an allergic inflammatory response, or a combination thereof. 
     
     
         13 . The method of  claim 12 , wherein the chronic obstructive pulmonary disease comprises emphysema or chronic bronchitis.