Method for inducing sustained immune response

Abstract

A method for promoting a sustained increased level of T-cell production in immunocompromised subjects in which method enkephalin peptides are administered according to an intermittent dose schedule. In particular, the method involves treatment of immunocompromised patients which includes the administration of enkephalin, either alone or in conjunction with other therapies, in an initial dosage regimen, with periodic booster dosages of enkephalin as necessary to maintain sustained immune system response.

I claim: 
     
         1 . A method of treating cortisol-induced immunosuppression in a subject by:
 treating said subject with an initial dosage regimen of enkephalin peptides;   discontinuing said initial dosage regimen with no further administration of said enkephalin peptides for at least four weeks; and   administering booster dosages of enkephalin peptides thereafter as necessary to reduce said cortisol-induced immunosuppression.   
     
     
         2 . The method of  claim 1 , wherein said initial dosage regimen comprises SEQ ID NO: 1, either alone or in conjunction with other therapies, wherein each dose in the initial dosage regimen is 1 to 250 μg/Kg bodyweight of the subject, and wherein said initial dosage regimen reduces said cortisol-induced immunosuppression,
 wherein said at least four weeks of discontinuing said initial dosage regimen with no further administration of said enkephalin peptide is for a period of 4 to 24 weeks, wherein the reduction in said cortisol-induced immunosuppression is sustained during said period in which said administration of said enkephalin peptide is discontinued, and wherein said reduction in said cortisol-induced immunosuppression comprises an elevated amount of at least one selected from the group consisting of IL2, gamma interferon, cytotoxic T cells, natural killer cells, CD38 cells and interleukin II receptor expression in comparison to a baseline value. 
 
     
     
         3 . A method of inhibiting cortisol-induced suppression of cytokine production in a subject by:
 treating said subject with an initial dosage regimen of enkephalin peptides;   discontinuing said initial dosage regimen with no further administration of said enkephalin peptides for at least four weeks; and   administering booster dosages of enkephalin peptides thereafter as necessary to maintain said cytokine production.   
     
     
         4 . The method of  claim 3 , wherein said initial dosage regimen comprises SEQ ID NO: 1, either alone or in conjunction with other therapies, wherein each dose in the initial dosage regimen is 1 to 250 μg/Kg bodyweight of the subject, and wherein said initial dosage regimen inhibits cortisol-induced suppression of cytokine production,
 wherein said at least four weeks of discontinuing said initial dosage regimen with no further administration of said enkephalin peptide is for a period of 4 to 24 weeks, and wherein the inhibition in said cortisol-induced suppression of cytokine production is maintained during said period in which said administration of said enkephalin peptide is discontinued. 
 
     
     
         5 . A method of inhibiting a cortisol-induced reduction of gene transcription of IL2 in a subject by:
 treating said subject with an initial dosage regimen of enkephalin peptides;   discontinuing said initial dosage regimen with no further administration of said enkephalin peptides for at least four weeks; and   administering booster dosages of enkephalin peptides thereafter as necessary to maintain said IL2 gene transcription.   
     
     
         6 . The method of  claim 5 , wherein said initial dosage regimen comprises SEQ ID NO: 1, either alone or in conjunction with other therapies, wherein each dose in the initial dose regimen is 1 to 250 μg/Kg bodyweight of the subject, and wherein said initial dosage regimen inhibits cortisol-induced reduction of gene transcription of IL2,
 wherein said at least four weeks of discontinuing said initial dosage regimen with no further administration of said enkephalin peptide is for a period of 4 to 24 weeks, and wherein the inhibition in said cortisol-induced reduction of gene transcription of IL2 is maintained during said period in which said administration of said enkephalin peptide is discontinued. 
 
     
     
         7 . A method of inhibiting cortisol-induced down-regulation of cytotoxic cells or NK lymphocytes in a subject by:
 treating said subject with an initial dosage regimen of enkephalin peptides;   discontinuing said initial dosage regimen with no further administration of said enkephalin peptides for at least four weeks; and   administering booster dosages of enkephalin peptides thereafter as necessary to maintain levels of said cytotoxic cells or NK lymphocytes.   
     
     
         8 . The method of  claim 7 , wherein said initial dosage regimen comprises SEQ ID NO: 1, either alone or in conjunction with other therapies, wherein each dose in the initial dosage regimen is 1 to 250 μg/Kg bodyweight of the subject, and wherein said initial dosage regimen inhibits cortisol-induced down-regulation of cytotoxic cells or NK lymphocytes,
 wherein said at least four weeks of discontinuing said initial dosage regimen with no further administration of said enkephalin peptide is for a period of 4 to 24 weeks, and wherein the inhibition in said cortisol-induced down-regulation of cytotoxic cells or NK lymphocytes is maintained during said period in which said administration of said enkephalin peptide is discontinued. 
 
     
     
         9 . The method of  claim 2 , wherein the dosage of enkephalin peptide during the initial dosage regimen is 20 μg/Kg bodyweight of the patient. 
     
     
         10 . The method of  claim 1 , wherein the need for periodic booster shots is determined by measuring the patient's reduction in said cortisol-induced immunsuppression from 4 to 16 weeks after cessation of the initial dosage regimen, and comparing the reduction in said cortisol-induced immunsuppression with both a baseline value and a response value measured at the end of the dosing schedule. 
     
     
         11 . The method of  claim 1 , wherein periodic booster dosages are given, as needed, up to 5 times a week for 1 to 4 weeks. 
     
     
         12 . The method of  claim 1 , wherein the booster dosage of enkephalin peptide after the initial dosage regimen ranges from 20 to 100 μg/Kg bodyweight. 
     
     
         13 . The method of  claim 1 , wherein the initial dosage regimen is 1-5 times per week over a 4-12 week period. 
     
     
         14 . The method of  claim 1 , wherein the other therapies include cytokine, antiviral, antibiotics, antifungal, antiparasite and anti-tumor therapies. 
     
     
         15 . The method of  claim 1 , wherein said initial dosage regime is once per week for 4 to 12 weeks. 
     
     
         16 . The method of  claim 3 , wherein the dosage of enkephalin peptide during the initial dosage regimen is 20 μg/Kg bodyweight of the patient. 
     
     
         17 . The method of  claim 3 , wherein said initial dosage regime is once per week for 4 to 12 weeks. 
     
     
         18 . The method of  claim 5 , wherein the dosage of enkephalin peptide during the initial dosage regimen is 20 μg/Kg bodyweight of the patient. 
     
     
         19 . The method of  claim 5 , wherein said initial dosage regime is once per week for 4 to 12 weeks. 
     
     
         20 . The method of  claim 7 , wherein the dosage of enkephalin peptide during the initial dosage regimen is 20 μg/Kg bodyweight of the patient. 
     
     
         21 . The method of  claim 7 , wherein said initial dosage regime is once per week for 4 to 12 weeks.