Methods and materials for treating inflammatory diseases

Abstract

The invention provides methods and materials related to the treatment of inflammatory diseases such as rheumatoid arthritis. Specifically, the invention provides methods and materials for treating inflammation by reducing production of an inflammatory cytokine such as IFN-γ, IL-1β, and TNF-α. The invention also provides methods and materials for identifying reagents that can be used to treat inflammatory diseases. Specifically, the invention provides non-human animals containing human synovial tissue as well as methods for using such non-human animals to determine the influence of various test reagents on the inflamed state of human synovial tissue.

What is claimed is:  
     
         1 . A method for treating an inflammatory disease, said method comprising: 
 a) identifying a host in need of an anti-inflammatory treatment, wherein said host has inflamed tissue, and    b) administering a pharmaceutically effective amount of an IL-16 polypeptide or an IL-16-mimicking molecule to said host under conditions such that the expression of an inflammatory cytokine in the region of said inflamed tissue is reduced.    
     
     
         2 . The method of  claim 1 , wherein said inflammatory disease is rheumatoid arthritis.  
     
     
         3 . The method of  claim 1 , wherein said IL-16-mimicking molecule comprises a recombinant HIV gp120 polypeptide.  
     
     
         4 . The method of  claim 1 , wherein said method comprises administering, to said host, a polypeptide selected from the group consisting of TGF-β1, IL-4 and IL-10.  
     
     
         5 . The method of  claim 1 , wherein said inflammatory cytokine comprises a cytokine selected from the group consisting of IFN-γ, IL-1β, and TNF-α.  
     
     
         6 . The method of  claim 1 , wherein said IL-16 polypeptide is recombinant human IL-16.  
     
     
         7 . The method of  claim 1 , wherein said host is a mammal.  
     
     
         8 . The method of  claim 7 , wherein said mammal is a human.  
     
     
         9 . A method of treating an inflammatory disease in a host, said method comprising providing nucleic acid to said host, wherein said nucleic acid encodes an IL-16 polypeptide and wherein said host expresses said IL-16 polypeptide from said nucleic acid such that the expression of an inflammatory cytokine is reduced in said host.  
     
     
         10 . The method of  claim 9 , wherein said inflammatory disease is rheumatoid arthritis.  
     
     
         11 . The method of  claim 9 , wherein said method comprises providing a second nucleic acid to said host, wherein said second nucleic acid encodes an immunosuppressive cytokine.  
     
     
         12 . The method of  claim 11 , wherein said immunosuppressive cytokine comprises a cytokine selected from the group consisting of TGF-β1, IL-4, and IL-10.  
     
     
         13 . The method of  claim 9 , wherein said inflammatory cytokine comprises a cytokine selected from the group consisting of IFN-γ, IL-1β, and TNF-α.  
     
     
         14 . The method of  claim 9 , wherein said IL-16 polypeptide is human IL-16.  
     
     
         15 . The method of  claim 9 , wherein said host is a mammal.  
     
     
         16 . The method of  claim 15 , wherein said mammal is a human.  
     
     
         17 . A method of treating an inflammatory disease in a host, said method comprising administering, to said host, cells that reduce the expression of an inflammatory cytokine.  
     
     
         18 . The method of  claim 17 , wherein said inflammatory disease is rheumatoid arthritis.  
     
     
         19 . The method of  claim 17 , wherein said cells are synovial tissue-derived CD8 +  T cells.  
     
     
         20 . The method of  claim 17 , wherein said cells express IL-16.  
     
     
         21 . The method of  claim 20 , wherein said IL-16 is human IL-16.  
     
     
         22 . The method of  claim 17 , wherein said cells express TGF-β1.  
     
     
         23 . The method of  claim 17 , wherein said cells contain exogenous nucleic acid encoding an IL-16 polypeptide.  
     
     
         24 . The method of  claim 17 , wherein said cells contain exogenous nucleic acid, wherein said exogenous nucleic acid encodes a polypeptide selected from the group consisting of TGF-β1, IL-4, and IL-10.  
     
     
         25 . The method of  claim 17 , wherein said inflammatory cytokine comprises a cytokine selected for the group consisting of IFN-γ, IL-1β, and TNF-α.  
     
     
         26 . The method of  claim 17 , wherein said host is a human.  
     
     
         27 . A pharmaceutical composition for treating an inflammatory disease in a host, said composition comprising an IL-16 polypeptide or an IL-16-mimicking molecule and an immunosuppressive cytokine, wherein the administration of said composition to said host reduces the expression of an inflammatory cytokine in said host.  
     
     
         28 . The composition of  claim 27 , wherein said inflammatory disease is rheumatoid arthritis.  
     
     
         29 . The composition of  claim 27 , wherein said IL-16 polypeptide is recombinant human IL-16.  
     
     
         30 . The composition of  claim 27 , wherein said IL-16-mimicking molecule comprises a recombinant HIV gp120 polypeptide.  
     
     
         31 . The composition of  claim 27 , wherein said immunosuppressive cytokine comprises a cytokine selected from the group consisting of TGF-β1, IL-4, and IL-10.  
     
     
         32 . The composition of  claim 27 , wherein said inflammatory cytokine comprises a cytokine selected from the group consisting of IFN-γ, IL-1β, and TNF-α.  
     
     
         33 . The composition of  claim 27 , wherein said host is a mammal.  
     
     
         34 . The composition of  claim 33 , wherein said mammal is a human.  
     
     
         35 . A non-human animal comprising human synovial tissue.  
     
     
         36 . The animal of  claim 35 , wherein said animal is a murine animal.  
     
     
         37 . The animal of  claim 35 , wherein said animal is immunocompromised.  
     
     
         38 . The animal of  claim 37 , wherein said immunocompromised animal is a SCID mouse.  
     
     
         39 . The animal of  claim 37 , wherein said immunocompromised animal is a recombination-activating gene-deficient animal.  
     
     
         40 . The animal of  claim 35 , wherein at least a portion of said human synovial tissue is located under the skin of said animal.  
     
     
         41 . The animal of  claim 35 , wherein at least a portion of said human synovial tissue is located in the back region of said animal.  
     
     
         42 . The animal of  claim 35 , wherein said human synovial tissue comprises inflamed human synovial tissue.  
     
     
         43 . The animal of  claim 42 , wherein said inflamed human synovial tissue is in a diffuse state of inflammation within said animal.  
     
     
         44 . The animal of  claim 42 , wherein said inflamed human synovial tissue is in a follicular state of inflammation within said animal.  
     
     
         45 . The animal of  claim 35 , wherein said human synovial tissue comprises diffusely vascularized human synovial tissue within said animal.  
     
     
         46 . The animal of  claim 35 , wherein said animal is a NOD/LtSz-Prkdc scid /J mouse comprising human synovial tissue derived from a rheumatoid arthritis patient.  
     
     
         47 . A method for identifying a treatment reagent that reduces inflammation, said method comprising: 
 a) administering a test reagent to a non-human animal having human synovial tissue, wherein at least a portion of said human synovial tissue is inflamed, and    b) determining if said administration of said test reagent reduces said inflammation, wherein a reduction in inflammation indicates that said test reagent is a treatment reagent.    
     
     
         48 . The method of  claim 47 , wherein said reduction in inflammation is determined by measuring IFN-y production by said human synovial tissue.  
     
     
         49 . An article of manufacture comprising packaging material and an IL-16 polypeptide or IL-16-mimicking molecule, wherein said packaging material comprises a label or package insert indicating that said IL-16 polypeptide or IL-16-mimicking molecule can be administered to a host for the purpose of treating an inflammatory disease.  
     
     
         50 . An article of manufacture comprising packaging material and nucleic acid encoding an IL-16 polypeptide, wherein said packaging material comprises a label or package insert indicating that said nucleic acid can be administered to a host for the purpose of treating an inflammatory disease.  
     
     
         51 . An article of manufacture comprising packaging material and cells that reduce the expression of an inflammatory cytokine, wherein said packaging material comprises a label or package insert indicating that said cells can be administered to a host for the purpose of treating an inflammatory disease.  
     
     
         52 . The use of an IL-16 polypeptide or an IL-16-mimicking molecule in the manufacture of a medicament for treating an inflammatory disease in a host in need of an anti-inflammatory treatment, wherein said host has inflamed tissue, and wherein administering a pharmaceutically effective amount of said medicament to said host reduces the expression of an inflammatory cytokine in the region of said inflamed tissue.  
     
     
         53 . The use of a nucleic acid in the manufacture of a medicament for treating an inflammatory disease in a host in need of an anti-inflammatory treatment, wherein said nucleic acid encodes an IL-16 polypeptide, wherein said host has inflamed tissue, and wherein administering said medicament to said host reduces the expression of an inflammatory cytokine in the region of said inflamed tissue.  
     
     
         54 . The use of cells in the manufacture of a medicament for treating an inflammatory disease in a host in need of an anti-inflammatory treatment, wherein said host has inflamed tissue, and wherein administering said medicament to said host reduces the expression of an inflammatory cytokine in the region of said inflamed tissue.