Biological marker for inflammation

Abstract

Inflammatory state in a subject is assayed by determining the level of expression of A 3 adenosine receptor (A 3 AR) in white blood cells (WBC), e.g. circulating WBCs, from the subject. A high level of expression of A 3 AR is indicative of an inflammatory state in the subject. This assay can be used for determining whether a patient known to have an inflammatory state should be treated with an A 3 AR agonist to reduce the inflammatory state. The patient will be so treated only if the level of A 3 AR in the WBC of the subject is above a predefined threshold, which is about twice the level of A 3 AR in WBC of healthy subjects. The inflammatory state may particularly be rheumatoid arthritis or uveitis.

1 . A therapeutic method, comprising:
 a. determining the level of A 3  adenosine receptor (A 3 AR) in a sample of white blood cells (WBCs) of a subject; and   b. treating the subject only if said level is above a predefined threshold which is about twice the level of A 3 AR in WBC of healthy subjects;   wherein
 (i) the subject is one that is known to have an inflammatory state, 
 (ii) the treating comprises administering an anti-inflammatory agent to the subject, and 
 (iii) the anti-inflammatory agent is an A 3 AR agonist; 
   wherein the treating step comprises treating the subject with an amount of A 3 AR agonist that is effective to reduce the inflammatory state in said subject.   
     
     
         2 . The method of  claim 1 , wherein the A 3 AR is N 6 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA). 
     
     
         3 . The method of  claim 1 , wherein the sample of WBC is taken from a subject before receiving the anti-inflammatory treatment. 
     
     
         4 . The method of  claim 1 , wherein the inflammatory state is the result of an autoimmune disease. 
     
     
         5 . The method of  claim 1 , wherein the inflammatory state is the result of rheumatoid arthritis or uveitis. 
     
     
         6 . The method of  claim 5 , wherein the A 3 AR is N 6 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA). 
     
     
         7 . A method for anti-inflammatory therapeutic treatment of a subject known to have an inflammatory state, the method comprising:
 a. determining the level of A 3  adenosine receptor (A 3 AR) in a sample of white blood cells (WBCs) of the subject; and   b. treating the subject with an anti-inflammatory agent only if the level is above a predefined threshold which is about twice the level of A 3 AR in WBC of healthy subjects;   wherein the anti-inflammatory agent is an A 3 AR agonist and the amount of the A 3 AR agonist is effective to reduce the inflammatory state in said subject.   
     
     
         8 . The method of  claim 7 , wherein the A 3 AR is N 6 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA). 
     
     
         9 . The method of  claim 7 , wherein the sample of WBC is taken from the subject before receiving the anti-inflammatory treatment. 
     
     
         10 . The method of  claim 7 , wherein the inflammatory state is the result of an autoimmune disease. 
     
     
         11 . The method of  claim 7 , wherein the inflammatory state is the result of rheumatoid arthritis or uveitis. 
     
     
         12 . The method of  claim 11 , wherein the A 3 AR is N 6 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA). 
     
     
         13 . In a method for anti-inflammatory therapeutic treatment of a subject known to have an inflammatory state, the method comprising treating the subject with an effective amount of an A3 adenosine receptor (A 3 AR) agonist,
 wherein the improvement comprises selecting the subject to receive the anti-inflammatory therapeutic treatment if determined to have a level of A 3  adenosine receptor (A 3 AR), in a sample of white blood cells (WBCs) of the subject, above a predefined threshold that is about twice the level of A 3 AR in WBC of healthy subjects, and withholding said treatment if determined to have a level of A 3 AR, in a sample of WBCs of the subject, below the predefined threshold.   
     
     
         14 . The method of  claim 13 , wherein the A 3 AR is N 6 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA). 
     
     
         15 . The method of  claim 13 , wherein the sample of WBCs is taken from a subject before receiving the anti-inflammatory treatment. 
     
     
         16 . The method of  claim 13 , wherein the inflammatory state is the result of an autoimmune disease. 
     
     
         17 . The method of  claim 13 , wherein the inflammatory state is the result of rheumatoid arthritis or uveitis. 
     
     
         18 . The method of  claim 17 , wherein the A 3 AR is N 6 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA).