Method of treatment and agents useful for same

Abstract

The present invention relates generally to a method for the treatment and prophylaxis of inflammatory conditions. The present invention is predicated in part on the identification of cells of the monocyte/macrophage lineage being critical for inflammation and, in particular, chronic inflammation. In accordance with the present invention, it is proposed that the reduction in levels of monocyte/macrophage-type cells and/or a reduction in the production of inflammatory and pro-inflammatory mediators by these cells, especially locally, is effective in reducing inflammatory conditions. The present invention further provides animal models useful for screening for reducing levels of monocyte/macrophage-type cells and/or reducing the production of inflammatory and pro-inflammatory mediators of these cells.

1 . A method for ameliorating the effects of inflammation in a subject, said method comprising administering an agent which inhibits or otherwise antagonizes the effects of a colony-stimulating factor on cells of the monocyte/macrophage lineage thereby reducing the level of proliferation, activation, growth and/or survival of said cells. 
     
     
         2 . (canceled) 
     
     
         3 . A method according to  claim 1  wherein the colony-stimulating factor is M-CSF, or GM-CSF. 
     
     
         4 . A method according to  claim 3  further comprising the co-administration of an agent which antagonizes u-PA and/or other inflammatory mediators produced by a cell of the monocyte/macrophage lineage. 
     
     
         5 . A method according to  claim 1  wherein the agent is a colony-stimulating factor receptor in soluble form, a binding protein of a colony-stimulating factor or an antibody to a colony-stimulating factor. 
     
     
         6 . A method according to  claim 1  wherein the agent is identified through natural product screening or screening of a chemical library. 
     
     
         7 . A method according to  claim 1  wherein the agent is internalized by the monocyte/macrophage. 
     
     
         8 - 28 . (canceled) 
     
     
         29 . The method according to  claim 1 , wherein the subject is human. 
     
     
         30 . The method according to  claim 1 , wherein said inflammation is selected from the group consisting of rheumatoid arthritis, inflammatory bowel disease, Crohns disease, type I diabetes, multiple sclerosis, psoriasis and chronic obstructive lung disease. 
     
     
         31 . The method according to  claim 30 , wherein said chronic obstructive lung disease is selected from the group consisting of asthma, chronic bronchitis, emphysema, and chronic obstructive airway disease. 
     
     
         32 . The method according to  claim 1 , wherein administering comprises intravenous, subcutaneous or local administration. 
     
     
         33 . The method according to  claim 5 , wherein the antibody specifically binds GM-CSF. 
     
     
         33 . The method according to  claim 5 , wherein the antibody specifically binds M-CSF. 
     
     
         34 . The method according to  claim 1 , wherein the administering is for a time and in an amount to inhibit or otherwise antagonize the effects of a colony-stimulating factor on said cells. 
     
     
         35 . The method according to  claim 5 , wherein the antibody is a monoclonal antibody. 
     
     
         36 . The method according to  claim 4 , wherein the co-administration of a further agent is administered simultaneously with the agent which antagonizes the effects of a colony-stimulating factor. 
     
     
         37 . The method according to  claim 4 , wherein the co-administration of a further agent is administered sequentially with the agent which antagonizes the effects of a colony-stimulating factor.