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 acute respiratory distress syndrome (ARDS), comprising: 
 administering an effective amount of an agent which is a protein whose sequence is at least 95% identical to the sequence of TFPI or ala-TFPI to an ARDS patient, whereby one or more symptoms of ARDS are improved.    
     
     
         2 . The method of  claim 1  wherein the agent is 98% identical by sequence to TFPI.  
     
     
         3 . The method of  claim 1  wherein the agent 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 98% identical by sequence to ala-TFPI.  
     
     
         6 . The method of  claim 1  wherein the agent differs from ala-TFPI in having a one amino acid residue substitution.  
     
     
         7 . The method of  claim 1  wherein the agent is a fragment of TFPI capable of inhibiting coagulation and further capable of inhibiting release of neutrophil elastase.  
     
     
         8 . The method of  claim 1  wherein the agent is TFPI.  
     
     
         9 . A method of preventing acute respiratory distress syndrome (ARDS), comprising: 
 administering an an effective amount of an agent which is a protein whose sequence is at least 95% identical to the sequence of TFPI or ala-TFPI to a patient at risk for developing ARDS, whereby the risk of developing ARDS is decreased.    
     
     
         10 . The method of  claim 9  wherein the agent is 98% identical by sequence to TFPI.  
     
     
         11 . The method of  claim 9  wherein the agent differs from TFPI in having a one amino acid residue substitution.  
     
     
         12 . The method of  claim 9  wherein the agent is ala-TFPI.  
     
     
         13 . The method of  claim 9  wherein the agent is 98% identical by sequence to ala-TFPI.  
     
     
         14 . The method of  claim 9  wherein the agent differs from ala-TFPI in having a one amino acid residue substitution.  
     
     
         15 . The method of  claim 9  wherein the agent is a fragment of ala-TFPI capable of inhibiting coagulation and further capable of inhibiting release of neutrophil elastase.  
     
     
         16 . The method of  claim 9  wherein the agent is TFPI.