Regulaton of cytokine synthesis and release

Abstract

Methods of treatment and prevention of diseases associated with release of neutrophil elastase and IL-8 by administration of TFPI, and analogs of TFPI are disclosed. Methods of determining efficacy of treatment with TFPI, patient's responsiveness to treatment with TFPI and the ultimate determination of patient prognosis are also disclosed.

1 . A method of treating a disease selected from the group consisting of: 
 (a) reperfusion injury; and    (b) arthritis;    comprising the step of administering an effective amount of an agent to a patient displaying the symptoms of said disease, wherein the agent is a protein whose sequence is at least 95% identical to the sequence of TFPI or ala-TFPI,    whereby at least one symptom of the disease is improved.    
     
     
         2 . The method of  claim 1  wherein the agent is a protein whose sequence is at least 98% identical to TFPI.  
     
     
         3 . The method of  claim 1  wherein the agent is a protein which differs from TFPI in having a one amino acid residue substitution.  
     
     
         4 . The method of  claim 1  wherein the agent is ala-TFPI.  
     
     
         5 . The method of  claim 1  wherein the agent is a protein whose sequence which is at least 98% identical to ala-TFPI.  
     
     
         6 . The method of  claim 1  wherein the agent is a protein which differs from ala-TFPI in having a one amino acid residue substitution.  
     
     
         7 . The method of  claim 1  wherein the agent is TFPI.  
     
     
         8 . A method of reducing the risk of a symptom of a disease selected from the group consisting of: 
 (a) arthritis; and    (b) reperfusion injury;    comprising the step of administering an effective amount of an agent to a patient at risk of contracting or developing further symptoms of said disease,    wherein the agent is a protein whose sequence which is at least 95% identical to the sequence of TFPI or ala-TFPI, whereby the risk of contracting or developing further symptoms of said disease is reduced.    
     
     
         9 . The method of  claim 8  wherein the agent is a protein whose sequence which is at least 98 % identical to TFPI.  
     
     
         10 . The method of  claim 8  wherein the agent is a protein which differs from TFPI in having a one amino acid residue substitution.  
     
     
         11 . The method of  claim 8  wherein the agent is ala-TFPI.  
     
     
         12 . The method of  claim 8  wherein the agent is a protein having a sequence which is at least 98% identical to ala-TFPI.  
     
     
         13 . The method of  claim 8  wherein the agent is a protein which differs from ala-TFPI in having a one amino acid residue substitution.  
     
     
         14 . The method of  claim 8  wherein the agent is TFPI.