ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS SUPPRESS PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN-VITRO AND IN-VIVO

It has been reported that angiotensin converting enzyme (ACE) inhibito rs 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 examin ed 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 mu g/ml)-induced in vitro TNF-alpha production, measured by b ioassay and enzyme-linked immunosorbent assay, was significantly inhib ited with captopril, delapril and cilazapril in a concentration of 10( -3) mol/l. A single, oral administration of captopril, delapril and ci lazapril at more than 10-fold doses of common clinical use in man sign ificantly inhibited LPS (2 mg/kg)-induced serum TNF-alpha activity in Balb/c mice. These results indicate that ACE inhibitors such as captop ril, delapril and cilazapril have an inhibitory effect on TNF-alpha pr oduction not only in vitro as previously reported, but also in vivo, a lthough relatively high concentrations and large doses were required i n this study.