Inhibiting DNA synthesis in T-lymphocytes, keratinocytes and TH2 cytokine production, comprises combined administration of dipeptidyl peptidase and alanyl-aminopeptidase inhibitors

摘要

Inhibiting the activation and proliferation (DNA synthesis) of human T-lymphocytes or mononuclear cells and the production of TH2 cytokines comprises combined administration of dipeptidyl peptidase IV (DP IV) inhibitors and alanyl-aminopeptidase (aminopeptidase N, APN) inhibitors. The DP IV and APN inhibitors may be replaced by enzymes with the same substrate specificity. Independent claims are also included for the following: (1) the combined use of DP IV and APN inhibitors for the (super-)additive inhibition of the activation and proliferation (DNA synthesis) of human epidermal and follicular keratinocytes and those in the transition region between the skin and mucosa; (2) the combined use of DP IV and APN inhibitors, X-Pro-aminopeptidase (APP) inhibitors, ACE inhibitors and/or prolyloligopeptidase (POP) inhibitors for the (super-)additive inhibition of the activation and proliferation (DNA synthesis) of human T-lymphocytes or mononuclear cells; and (3) pharmaceutical preparations containing DP IV and APN inhibitors (or enzymes with the same substrate specificity) and optionally APP, ACE and/or POP inhibitors. ACTIVITY : Antiinflammatory; Immunosuppressive; Antiarteriosclerotic; Antipsoriatic; Dermatological; Virucide; Cytostatic. MECHANISM OF ACTION : Dipeptidyl peptidase inhibitor; Alanyl-aminopeptidase inhibitor; X-Pro-aminopeptidase inhibitor; Acetylcholine esterase inhibitor; Prolyloligopeptidase inhibitor. Human peripheral T-lymphocytes were incubated for 72 hours in the presence of Lys[Z(NO 2)]-thiazolidide (DP IV inhibitor) and actinoin (APN inhibitor), after which 3[H]-thymidine incorporation was measured to determine the extent of DNA synthesis. Results showed a dosage-dependent (super-)additive inhibition of DNA synthesis.