Uses of mammalian cytokine; related reagents

Abstract

Provided are methods of treatment for skin disorders. In particular, treatment, the skin disorders are generally inflammatory skin disorders, including improper wound healing. Provided are methods of using of a cytokine molecule.

What is claimed is: 
     
         1 . A method of treating or improving healing comprising administering to a subject an effective amount of an agonist or antagonist of IL-23. 
     
     
         2 . The method of  claim 1  wherein the agonist or antagonist comprises:
 a) a polypeptide of IL-23, or a derivative or variant thereof; 
 b) a binding composition derived from an antibody that specifically binds to IL-23 or to IL-23R; or 
 c) a nucleic acid encoding a polypeptide of IL-23, or a derivative or variant thereof. 
 
     
     
         3 . The method of  claim 2 , wherein the derivative or variant comprises an IL-23 hyperkine. 
     
     
         4 . The method of  claim 1 , wherein the agonist comprises a complex of:
 a) a mature sequence of SEQ ID NO:10; and   b) a mature sequence of SEQ ID NO:12.   
     
     
         5 . The method of  claim 2 , wherein the nucleic acid further comprises an expression vector. 
     
     
         6 . The method of  claim 1 , wherein the healing is:
 a) of a skin or cutaneous wound;   b) of an ulcer or graft; or   c) improper healing.   
     
     
         7 . The method of  claim 1 , wherein the treating or improving increases:
 a) a pressure required to break a healed or healing wound;   b) a stiffness of a healed or healing wound;   c) a rate of healing of a wound;   d) a granulation layer thickness of a healed or healing wound;   e) recruitment of a cell to or towards a wound; or   f) antimicrobial activity.   
     
     
         8 . The method of  claim 7 , wherein the cell is:
 a) a CD11b + , MHC Class II +  cell;   b) a monocyte/macrophage; or   c) a CD31 +  endothelial cell.   
     
     
         9 . The method of  claim 7 , wherein the recruitment is in or towards a granulation tissue. 
     
     
         10 . The method of  claim 7 , wherein:
 a) the increased wound breaking pressure is about a 15% or about a 20% increase in wound breaking pressure; or   b) the increased stiffness is about a 15% or about a 20% increase in stiffness.   
     
     
         11 . The method of  claim 1 , wherein the treating or improving comprises increased:
 a) angiogenesis; or   b) immune surveillance.   
     
     
         12 . The method of  claim 11 , wherein:
 a) the increased angiogenesis is mediated by ICAM-1 or -2; or   b) the increased immune surveillance is mediated by dendritic cells.   
     
     
         13 . The method of  claim 1 , wherein the treating or improving comprises increased expression of a nucleic acid or protein of:
 a) a cytokine in addition to IL-23;   b) a signaling molecule;   c) an anti-microbial molecule;   d) a protease or protease inhibitor; or   e) a molecule of the extracellular matrix.   
     
     
         14 . The method of  claim 13 , wherein the cytokine nucleic acid or protein is IL-17, IL-6, IL-19, GRO-alpha, or GM-CSF. 
     
     
         15 . The method of  claim 13 , wherein the gene or protein is:
 a) lactoferrin;   b) DEC-205;   c) LD50;   d) nitric oxide synthase; or   e) secretory leukoprotease inhibitor; or   f) CD40L.   
     
     
         16 . The method of  claim 1 , wherein the antagonist comprises:
 a) a nucleic acid;   b) a blocking antibody to IL-23 or to IL-23R; or   c) a soluble receptor derived from an extracellular part of IL-23R.   
     
     
         17 . The method of  claim 16 , wherein the nucleic acid comprises:
 a) an anti-sense nucleic acid; or   b) interference RNA.   
     
     
         18 . An agonist of IL-23 derived from the binding site of an antibody that specifically binds to an IL-23 receptor. 
     
     
         19 . The agonist of  claim 18  that is:
 a) a polyclonal antibody; 
 b) a monoclonal antibody; 
 c) an Fab, Fv, or F(ab′) 2  fragment; 
 d) humanized; 
 e) a peptide mimetic; or 
 f) detectably labeled. 
 
     
     
         20 . The agonist of  claim 18 , comprising a complex of:
 a) a polypeptide of the mature sequence of SEQ ID NO:10; and   b) a polypeptide of the mature sequence of SEQ ID NO:12.   
     
     
         21 . The agonist of  claim 18 , comprising a complex of:
 a) two polypeptides of the mature sequence of SEQ ID NO:10; and   b) two polypeptides of the mature sequence of SEQ ID NO:12.   
     
     
         22 . The agonist of  claim 18 , wherein contact of the agonist to a cell expressing hIL-23R and hIL-12beta1 results in an increase in proliferation of the cell. 
     
     
         23 . A kit comprising the agonist of  claim 18  and:
 a) a compartment; or 
 b) instructions for use or disposal.