Methods and compositions for delivering interleukin-1 receptor antagonist

Abstract

Methods, systems, and compositions related to generating and using a solution rich in interleukin-1 receptor antagonist are provided. Methods include contacting a liquid comprising white blood cells with a solid extraction material and stimulating with an electromagnetic field to activate production of interleukin-1 receptor antagonist. The interleukin-1 receptor antagonist can be separated from the solid extraction material. Methods for treating a site of inflammation in a patient include administering the solution rich in interleukin-1 receptor antagonist to the site of inflammation.

1 - 91 . (canceled) 
     
     
         92 . A method of treating inflammation in a subject comprising:
 administering to a site of inflammation a composition rich in interleukin-1 receptor antagonist, the composition comprising
 interleukin-1 receptor antagonist; and 
 soluble tumor necrosis factor receptor; 
 wherein the interleukin-1 receptor antagonist and the soluble tumor necrosis factor receptors are derived from the same subject and the concentrations of interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor are each greater than found in whole blood or plasma. 
   
     
     
         93 . The method of  claim 92 , wherein the inflammation is associated with osteolysis. 
     
     
         94 . The method of  claim 92 , wherein the inflammation is associated with osteoarthritis. 
     
     
         95 . The method of  claim 92 , further comprising administering fibrinogen, thrombin, calcium, or a combination thereof to the site of inflammation. 
     
     
         96 . The method of  claim 92 , wherein the concentration of the interleukin-1 receptor antagonist in the composition rich in interleukin-1 receptor antagonist is at least about 5,000 times greater than the concentration of the soluble tumor necrosis factor receptor. 
     
     
         97 . The method of  claim 92 , wherein the concentration of interleukin-1 receptor antagonist in the composition rich in interleukin-1 receptor antagonist is at least about 10,000 times higher than found in whole blood. 
     
     
         98 . The method of  claim 92 , wherein the concentration of interleukin-1 receptor antagonist in the composition rich in interleukin-1 receptor antagonist is about 30,000 pg/mL to about 110,000 pg/mL. 
     
     
         99 . The method of  claim 92 , wherein the soluble tumor necrosis factor receptor in the composition rich in interleukin-1 receptor antagonist comprises soluble tumor necrosis factor receptor I, soluble tumor necrosis factor receptor II, or both. 
     
     
         100 . The method of  claim 92 , further comprising interleukin-1a, wherein the concentration of interleukin-1 receptor antagonist in the composition rich in interleukin-1 receptor antagonist is at least about 10,000 times higher than the concentration of interleukin-1a. 
     
     
         101 . The method of  claim 92 , wherein the composition rich in interleukin-1 receptor antagonist further comprises viable white blood cells, lysed white blood cells, or both. 
     
     
         102 . The method of  claim 92 , wherein the composition rich in interleukin-1 receptor antagonist further comprises platelets. 
     
     
         103 . The method of  claim 92 , wherein the total protein concentration in the composition rich in interleukin-1 receptor antagonist is greater than that of whole blood. 
     
     
         104 . The method of  claim 92 , further comprising:
 contacting a liquid comprising white blood cells with a solid extraction material; and   separating the composition rich in interleukin-1 receptor antagonist from the solid extraction material, wherein the concentration of interleukin-1 receptor antagonist in the composition rich in interleukin-1 receptor antagonist is greater than the concentration of interleukin-1 receptor antagonist in the liquid prior to contacting the liquid with the solid extraction material.   
     
     
         105 . The method of  claim 104 , further comprising subjecting the liquid to an electromagnetic field while contacting the liquid with the solid extraction material. 
     
     
         106 . The method of  claim 104 , wherein the solid extraction material comprises a member selected from the group consisting of corundum, quartz, titanium, dextran, agarose, polystyrene, polyethylene, polyvinyl chloride, polypropylene, polyacrylamide, and combinations thereof. 
     
     
         107 . The method of  claim 104 , wherein the liquid comprising white blood cells comprises at least one of whole blood, platelet-rich plasma, bone marrow aspirate, adipose tissue, fractions thereof, and a white blood cell fraction derived from a tissue selected from the group consisting of whole blood, bone marrow aspirate, and combinations thereof. 
     
     
         108 . The method of  claim 107 , wherein the white blood cell fraction is prepared by a process comprising:
 loading the tissue into a tube comprising a buoy disposed in the tube, wherein the buoy has a density such that the buoy is operable to reach an equilibrium position upon centrifugation of the tissue in the tube, the equilibrium position being between a first fraction and a second fraction comprising white blood cells, the second fraction having a concentration of white blood cells greater than the concentration of white blood cells in the first fraction;   centrifuging the tube so that the buoy defines an interface between the first fraction and the second fraction; and   removing the white blood cell fraction.   
     
     
         109 . The method of  claim 108 , further comprising subjecting the liquid to an electromagnetic field, wherein the tube further comprises
 an isolator operable to define an interface between the second fraction and a fraction comprising platelet-poor plasma; and   polyacrylamide beads as the solid extraction material disposed between the buoy and the isolator;   wherein the second fraction contacts the polyacrylamide beads following the centrifuging, and wherein the subjecting the liquid to an electromagnetic field is performed while the second fraction is in contact with the polyacrylamide beads.   
     
     
         110 . The method of  claim 107 , wherein the white blood cell fraction is prepared by a process comprising:
 loading the tissue into a separator comprising two buoys, the buoys being operable to separate the blood into three or more fractions including a fraction comprising white blood cells;   centrifuging the separator to create the fraction comprising white blood cells; and   extracting the white blood cell fraction from the separator.   
     
     
         111 . The method of  claim 104 , wherein the liquid comprising white blood cells is a liquid comprising concentrated white blood cells made by a method comprising
 passing a tissue or tissue fraction comprising white blood cells through a size exclusion filter,   mixing a tissue or tissue fraction comprising white blood cells with magnetic beads that are coupled to an antibody operable to bind mononuclear leukocytes, and collecting mononuclear leukocytes bound by the antibody for use as the liquid comprising concentrated white blood cells, or   a combination thereof.