title: Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factor-alpha in vitro and in vivo.
abstract: It has been reported that angiotensin converting enzyme (ACE) inhibitors have beneficial effects on insulin resistance and congestive heart failure, in which elevations of serum tumor necrosis factor-alpha (TNF-alpha) level have been indicated. Therefore, in this study, we examined effect of ACE inhibitors on TNF-alpha production both in vitro and in vivo by using human blood mononuclear cells and mice, respectively. LPS (20 micrograms/ml)-induced in vitro TNF-alpha production, measured by bioassay and enzyme-linked immunosorbent assay, was significantly inhibited with captopril, delapril and cilazapril in a concentration of 10(-3) mol/l. A single, oral administration of captopril, delapril and cilazapril at more than 10-fold doses of common clinical use in man significantly inhibited LPS (2 mg/kg)-induced serum TNF-alpha activity in Balb/c mice. These results indicate that ACE inhibitors such as captopril, delapril and cilazapril have an inhibitory effect on TNF-alpha production not only in vitro as previously reported, but also in vivo, although relatively high concentrations and large doses were required in this study.
authors.affiliation: Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukuzawa
authors.forename: J
authors.initials: J
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Sagara
authors.forename: G
authors.initials: G
authors.lastname: Muto
authors.forename: Y
authors.initials: Y
authors.lastname: Muto
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
authors.forename: S
authors.initials: S
authors.lastname: Miyaguchi
authors.forename: X L
authors.initials: XL
authors.lastname: Qiang
authors.forename: Y
authors.initials: Y
authors.lastname: Sakata
authors.forename: T
authors.initials: T
authors.lastname: Nakazawa
authors.forename: F
authors.initials: F
authors.lastname: Ikehata
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: T
authors.initials: T
authors.lastname: Toyota
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002216:Captopril