Application of aminopeptidases inhibitors and pharmaceutical preparations containing same

摘要

The use of inhibitor(s) (I) of alanyl-aminopeptidases (and/or enzymes of the same substrate specificity) is claimed for: (a) induction of production of transforming growth factor-beta 1 (TGF-beta 1) and expression of TGF-beta 1 in and/or on Treg cells; (b) treatment and/or prophylaxis of autoimmune diseases, allergies of type I (Gell and Coombs), hay fever or allergies of type II, III or IV; or (c) suppression of transplant rejection. Independent claims are included for: (1) use of (I) for the production of medicaments or pharmaceutical preparations for use as in (a), (b) or (c) above; and (2) pharmaceutical preparations containing (I), pharmaceutical carriers, additives and/or auxiliaries and optionally one or more of peptide fragments of autoantigens (or synthetic analogs) and/or specific antigenic fragments of pathogenic microorganisms. ACTIVITY : Immunosuppressive; Antiallergic; Antiinflammatory; Antirheumatic; Antiarthritic; Dermatological; Neuroprotective; Antidiabetic; Antiulcer; Antipsoriatic; Nephrotropic; Vasotropic; Antithyroid; Antianemic; Antiarteriosclerotic; Antiasthmatic. MECHANISM OF ACTION : Alanyl-aminopeptidase inhibitor; TGF-1beta production and expression inducer in and/or on Treg cells. In tests for the induction of gene expression of TGF-beta 1 in human regulatory T-lymphocytes, the T-cells were incubated for 24 hours (i) without additives, (ii) in presence of phytohemagglutinin (PHA; mitogen) and phorbol myristate acetate (PMA; proliferation stimulant) or (iii) PHA, PMA and phebestin (Ia). The TGF-beta 1-mRNA content (determined by reverse transcriptase PCR, in relative units) was (i) ca. 80, (ii) ca. 100 and (iii) ca. 1850.