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) 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.
Fukuzawa
M
M
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Satoh
J
J
Sagara
M
M
Muto
G
G
Muto
Y
Y
Nishimura
S
S
Miyaguchi
S
S
Qiang
X L
XL
Sakata
Y
Y
Nakazawa
T
T
Ikehata
F
F
Ohta
S
S
Toyota
T
T
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*
D000806:Angiotensin-Converting Enzyme Inhibitors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002216:Captopril