Effects of the angiotensin converting enzyme inhibitor captopril on experimental autoimmune encephalomyelitis.
Angiotensin converting enzyme (ACE)1 mediates inflammation, participates in T cell stimulation by certain antigenic peptides, and influences the permeability of the blood brain barrier (BBB). ACE is elevated in multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS), characterized by increased BBB permeability. ACE inhibitor captopril suppresses certain immune functions and inhibits inflammatory or autoimmune diseases. We studied the effect of captopril on Lewis rat EAE, an animal model of MS. Fourteen rats with EAE were treated with captopril 30 mg/kg daily from immunization to day 21 post-immunization, and compared with 14 untreated rats. Severity scores and lymphocyte reactivity to myelin basic protein and mitogen were measured. There was a statistically significant (p < 0.05) difference between the mean and cumulative clinical scores of captopril-treated and untreated animals. Lymphocytes from captopril treated EAE rats at the peak of disease severity had diminished responses to MBP and concanavalin A. The data suggest a significant beneficial effect of captopril in Lewis rat EAE. Further studies including other inhibitors of ACE or of other peptidases with immune, inflammatory or BBB role, may identify potentially valuable immunopharmacologic agents.
Constantinescu
C S
CS
Department of Neurology, University of Pennsylvania, Philadelphia 19104, USA.
Ventura
E
E
Hilliard
B
B
Rostami
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D002216:Captopril / Q000627:therapeutic use*; D003208:Concanavalin A / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000941:Antigens; D007166:Immunosuppressive Agents; D003208:Concanavalin A; D002216:Captopril