title: Modulation of the kallikrein/kinin system by the angiotensin-converting enzyme inhibitor alleviates experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Bradykinin is the end-product of the kallikrein/kinin system, which has been recognized as an endogenous target for combating CNS inflammation. Angiotensin-converting enzyme (ACE) inhibitors influence the kallikrein/kinin system and reportedly have immunomodulatory characteristics. The objectives of this study were to determine whether bradykinin is involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and whether bradykinin control by the ACE inhibitor could be a therapeutic target in MS. The ACE inhibitor enalapril (1·0 or 0·2 mg/kg/day) was administered orally to EAE mice and the serum levels of bradykinin and cytokines in EAE mice were analysed. As a result, the administration of enalapril increased serum bradykinin levels, decreased the clinical and pathological severity of EAE and attenuated interleukin-17-positive cell invasion into the CNS. Additionally, bradykinin receptor antagonist administration reduced the favourable effects of enalapril. Our results suggest that bradykinin is involved in the pathomechanism underlying CNS inflammation in EAE, possibly through inhibiting cell migration into CNS. Control of the kallikrein/kinin system using ACE inhibitors could be a potential therapeutic strategy in MS.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Uzawa
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: J
authors.initials: J
authors.lastname: Taniguchi
authors.forename: S
authors.initials: S
authors.lastname: Kuwabara
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003711:Demyelinating Diseases / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007610:Kallikreins / Q000378:metabolism*; D051379:Mice; D009103:Multiple Sclerosis / Q000378:metabolism; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; C120984:R 715; D004656:Enalapril; D007610:Kallikreins; D001920:Bradykinin
keywords: angiotensin-converting enzyme inhibitor; bradykinin; enalapril; experimental autoimmune encephalomyelitis; multiple sclerosis