Methods and compositions for promoting the maturation of monocytes

Abstract

Disclosed is a method of promoting the maturation of monocytes comprising the administration of a reactive oxygen species (ROS) inhibitor or scavenger and at least one monocyte maturation-promoting agent. A composition for promoting the maturation of monocytes is likewise disclosed. The pharmaceutical composition includes a compound effective to promote the maturation of monocytes and a ROS inhibitor or scavenger combined in a pharmaceutically acceptable carrier.

What is claimed is:  
     
         1 . A method of promoting the maturation of monocytes comprising administering to a population of cells including monocytes at least one monocyte maturation-promoting agent and at least one compound selected from the group consisting of a ROS production and release inhibitor or a ROS scavenger.  
     
     
         2 . The method of  claim 1 , wherein said monocyte maturation promoting agent is selected from the group consisting of IL-1, GM-CSF, IL-3, IL-6, TNF-α, G-CSF, M-CSF, IL-4, IL-12, IL-15, and IL-18.  
     
     
         3 . The method of  claim 1 , wherein said compound and said at least one monocyte maturation-promoting agent are administered in vivo.  
     
     
         4 . The method of  claim 1 , wherein the administration of said compound and said at least one monocyte maturation-promoting agent is performed simultaneously.  
     
     
         5 . The method of  claim 1 , wherein the administration of said compound is performed within 24 hours of the administration of said at least one monocyte maturation-promoting agent.  
     
     
         6 . The method of  claim 1 , wherein said at least one monocyte maturation-promoting agent is administered in a dose of from about 500 to about 1,000,000 U/kg/day.  
     
     
         7 . The method of  claim 1 , wherein said at least one monocyte maturation-promoting agent is administered in a dose of from about 3,000 to about 200,000 U/kg/day.  
     
     
         8 . The method of  claim 1 , wherein said compound is administered in a dose of from about 0.1 to about 20 mg/day.  
     
     
         9 . A method of augmenting the activity of a monocyte maturation enhancing agent comprising: 
 a) administering a compound selected from the group consisting of a ROS inhibitor or a ROS scavenger in a pharmaceutically acceptable form; and    b) administering said monocyte maturation enhancing agent, wherein the monocyte maturation effects of said agent are augmented.    
     
     
         10 . The method of  claim 9 , wherein said agent is a cytokine.  
     
     
         11 . The method of  claim 10 , wherein the cytokine is selected from the group consisting of IL-1, GM-CSF, IL-3, IL-4, IL-6, TNF-≢, G-CSF, M-CSF, IL-12, IL-15, and IL-18.  
     
     
         12 . The method of  claim 10 , wherein the cytokine is GM-CSF.  
     
     
         13 . The method of  claim 10 , wherein the cytokine is administered in the dosage of from about 500 to about 1,000,000 U/kg/day.  
     
     
         14 . The method of  claim 10 , wherein the cytokine is administered in the dosage of from about 3,000 to about 200,000 U/kg/day.  
     
     
         15 . The method of  claim 9 , wherein the administration of said compound and said at least one monocyte maturation-promoting agent is performed simultaneously.  
     
     
         16 . The method of  claim 9 , wherein the administration of said compound is performed within 24 hours of the administration of said at least one monocyte maturation-promoting agent.  
     
     
         17 . A method of treating a subject having cancer comprising: 
 a) identifying a subject having cancer,    b) administering at least one monocyte maturation-promoting agent; and    c) administering a compound selected from the group consisting of a ROS inhibitor or a ROS scavenger in a pharmaceutically acceptable form.    
     
     
         18 . The method of  claim 17 , wherein said at least one monocyte maturation-promoting agent is a cytokine selected from the group consisting of IL-1, GM-CSF, IL-3, IL-4, IL-6, TNF-α, G-CSF, M-CSF, IL-12, IL-15 and IL-18.  
     
     
         19 . The method of  claim 17 , wherein said at least one monocyte maturation-promoting agent is administered in a dose of from about 500 to about 1,000,000 U/kg/day.  
     
     
         20 . The method of  claim 17 , wherein said at least one monocyte maturation-promoting agent is administered in a dose of from about 3,000 to about 200,000 U/kg/day.  
     
     
         21 . The method of  claim 17 , wherein the administration of said at least one monocyte maturation promoting agent and said compound is performed simultaneously.  
     
     
         22 . The method of  claim 17 , wherein the administration of said at least one monocyte-maturation promoting agent is performed within 24 hours of the administration of said compound.  
     
     
         23 . A method of treating a subject having a chronic infection comprising: 
 a) identifying a subject suffering from a chronic infection;    b) administering at least one monocyte maturation-promoting agent, wherein said monocyte maturation-promoting agent promotes the maturation of monocytes; and    c) administering a compound selected from the group consisting of a ROS inhibitor or a scavenger in a pharmaceutically acceptable form.    
     
     
         24 . The method of  claim 23 , wherein said at least one monocyte maturation-promoting agent is a cytokine selected from the group consisting of IL-1, GM-CSF, IL-3, IL-4, IL-6, TNF-α, G-CSF, M-CSF, IL-12, IL-15, and IL-18.  
     
     
         25 . The method of  claim 23 , wherein said chronic infection is caused by a virus.  
     
     
         26 . The method of  claim 25 , wherein the virus is selected from the group consisting of adenovirus, cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1, herpes simplex virus 2, human herpesvirus 6, varicella-zoster virus, hepatitis B virus, hepatitis D virus, papilloma virus, parvovirus B19, polyomavirus BK, polyomavirus JC, hepatitis C virus, measles virus, rubella virus, human immunodeficiency virus (HIV), human T cell leukemia virus I, and human T cell leukemia virus II.  
     
     
         27 . The method of  claim 23 , wherein said chronic infection is caused by a parasite.  
     
     
         28 . The method of  claim 27 , wherein said parasite is selected from the group consisting of Leishmania, Toxoplasma, Trypanosoma, Plasmodium, Schistosoma, and Encephalitozoon.  
     
     
         29 . The method of  claim 23 , wherein the administration of said at least one monocyte-maturation promoting agent and said compound are performed simultaneously.  
     
     
         30 . The method of  claim 23 , wherein the administration of said compound is performed within 24 hours of the administration of said at least one monocyte-maturation promoting agent.  
     
     
         31 . A pharmaceutical composition comprising: 
 a compound effective to promote the maturation of monocytes and a compound selected from the group consisting of a ROS inhibitor or a ROS scavenger combined in a pharmaceutically acceptable carrier.    
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein said compound effective to promote the maturation of monocytes is selected from the group consisting of IL-1, GM-CSF, IL-3, IL-4, IL-6, TNF-α, G-CSF, M-CSF, IL-12, IL-15, and IL-18.  
     
     
         33 . The pharmaceutical composition of  claim 31 , wherein said compound effective to promote the maturation of monocytes is GM-CSF.  
     
     
         34 . The pharmaceutical composition of  claim 31 , wherein said ROS inhibitor is selected from the group consisting of histamine, histamine dihydrochloride, histamine phosphate, other histamine salts, esters, prodrugs, histamine receptor agonists, serotonin, 5HT agonists, and an endogenous histamine releasing compound.  
     
     
         35 . The pharmaceutical composition of  claim 31 , wherein said ROS scavenger is selected from the group consisting of catalase, glutathione peroxidase, ascorbate peroxidase, vitamin A, vitamin E, or vitamin C.  
     
     
         36 . A method of manufacture of a pharmaceutical composition comprising providing a compound selected from the group consisting of a ROS inhibitor or a ROS scavenger and at least one monocyte maturation-promoting compound in a pharmaceutically acceptable form.  
     
     
         37 . The method of  claim 36 , wherein said at least one monocyte maturation-promoting compound is selected from the group consisting of IL-1, GM-CSF, IL-3, IL-4, IL-6, TNF-α, G-CSF, M-CSF, IL-12, IL-15, and IL-18.  
     
     
         38 . The method of  claim 36 , wherein said monocyte maturation-promoting compound is GM-CSF.