Modulation of the kallikrein/kinin system by the angiotensin‐converting enzyme inhibitor alleviates experimental autoimmune encephalomyelitis

Summary 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 .