Methods for preventing strokes by inducing tolerance to E-selectin

Abstract

The present invention provides a method for reducing stroke-related tissue damage by treating a mammal with E-selectin. Preferably, this treatment induces E-selectin tolerance in the mammal. Another aspect of the invention is a method for inducing E-selectin tolerance in a mammal through intranasal administration of E-selectin, preferably including booster administrations. The present methods are especially adapted for use in patients at increased risk of stroke or who may become at increased risk of stroke.

1 . A method for reducing the likelihood of stroke in a patient, said method comprising administering E-selectin in an amount effective to induce E-selectin tolerance in the patient.  
   
   
       2 . The method of  claim 1 , wherein E-selectin tolerance is induced by a first intranasal administration of E-selectin comprising a first series of intranasal administrations of E-selectin.  
   
   
       3 . The method of  claim 2 , wherein the first series of intranasal administrations of E-selectin is followed by a booster administration of E-selectin after at least two weeks from the first intranasal administration of E-selectin.  
   
   
       4 . A method for inducing E-selectin tolerance in a mammal to reduce blood vessel inflammation or an immune response within a blood vessel comprising intranasal administration of E-selectin to the mammal.  
   
   
       5 . The method of  claim 4 , wherein inducing E-selectin tolerance treats vascular disease, coronary artery disease, lung injury, psoriasis, contact dermatitis, inflammatory bowel disease, arthritis, multiple sclerosis and combinations thereof.  
   
   
       6 . A method for reducing the likelihood of damage to brain tissue resulting from blood vessel obstruction in a mammal, said method comprising a series of E-selectin administrations to mucosal surfaces of the mammal in an amount of E-selectin that is effective to induce E-selectin tolerance in the mammal.  
   
   
       7 . A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and an effective amount of E-selectin, wherein the formulation is formulated for mucosal administration of E-selectin.  
   
   
       8 . The pharmaceutical formulation of  claim 7 , wherein the E-selectin comprises soluble E-selectin.  
   
   
       9 . The pharmaceutical formulation of  claim 7 , wherein the E-selectin comprises E-selectin lectin, epidermal growth factor and complement repeat modules.  
   
   
       10 . The pharmaceutical formulation of  claim 7 , wherein the E-selectin comprises E-selectin lectin, EGF, CR1 and CR2 domains.  
   
   
       11 . The pharmaceutical formulation of  claim 7 , wherein the mucosal administration is enteral, oral, or inhalable.  
   
   
       12 . The pharmaceutical formulation of  claim 7 , wherein the formulation is formulated for intranasal administration of E-selectin.  
   
   
       13 . The pharmaceutical formulation of  claim 7 , wherein the formulation is formulated as an aerosol.  
   
   
       14 . The pharmaceutical formulation of  claim 13 , wherein the aerosol is a dry aerosol.  
   
   
       15 . The pharmaceutical formulation of  claim 13 , wherein the aerosol is an atomized aqueous solution.  
   
   
       16 . The pharmaceutical formulation of  claim 7 , wherein the E-selectin is human E-selectin.  
   
   
       17 . The pharmaceutical formulation of  claim 7 , wherein the E-selectin is other than human E-selectin.  
   
   
       18 . The pharmaceutical formulation of  claim 7 , wherein the E-selectin is rat E-selectin.  
   
   
       19 . The pharmaceutical formulation of  claim 7 , wherein an effective amount of E-selectin is sufficient to promote tolerance to E-selectin in a mammal.  
   
   
       20 . The pharmaceutical formulation of  claim 7 , wherein an effective amount of E-selectin is sufficient to promote bystander-effect tolerance to E-selectin in a mammal.  
   
   
       21 . The pharmaceutical formulation of  claim 7 , wherein an effective amount of E-selectin is about 0.005 mg to about 500 mg.  
   
   
       22 . The pharmaceutical formulation of  claim 7 , wherein an effective amount of E-selectin is about 5 μg to about 50 mg.