| abstract |
The invention relates to a method which permits, owing to the simultaneous and joint inhibition of the enzyme activities of (I) alanyl-aminopeptidase and dipeptidyl-peptidase IV, (II) of the dipeptidyl-peptidase IV and the angiotensin-converting enzyme, (III) of the dipeptidyl-peptidase IV and prolyl-oligopeptidase, and of (IV) the dipeptidyl-peptidase IV and the X-Pro-aminopeptidase, to inhibit DNA synthesis and thus the proliferation of mononuclear cells as well as of T cells to an extent which cannot be obtained by the individual application of said enzyme inhibitors even when used in higher doses. Although the above-mentioned inhibitors influence the same process, namely DNA synthesis and thus the proliferation of immune cells, this effect is not complete and not long-lasting when the inhibitors are used individually. The functional overlapping of the enzymatic activities results, as is supported by the experimental data, in an additive/super-additive inhibitory effect on DNA synthesis and the proliferation resulting from the simultaneous inhibition of a plurality of the above enzymes. The invention shows that the simultaneous application of inhibiting substances of the above-mentioned enzymes or of corresponding preparations and forms of administration is suitable for the therapy of autoimmune diseases and chronic diseases with an inflammatory genesis as well as for the treatment of post-transplant rejection episodes. |