Suppression of Endotoxin-Induced Renal Tumor Necrosis Factor-α and Interleukin-6 mRNA by Renin-Angiotensin System Inhibitors

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The present study was designed to clarify the role of angiotensin II (Ang II) in modulating renal tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) production and to investigate the effect of one dose of Ang II inhibitor on cytokines production following lipopolysaccharide (LPS) to cause endotoxemia. Two studies were performed: 1) Ang II was infused intravenously at a rate of 0.2 μg/kg per minute for 4 h in rats and then kidneys were collected to assay TNF-α and IL-6 mRNA levels; 2) Four-week-old Wistar rats pre-treated with angiotensin-converting enzyme inhibitor, enalapril, or type I Ang II-receptor antagonist, TCV-116, were injected with LPS (0.1, 0.5, 1.0 mg, i.p.), and then 2 or 4 h later, kidneys were collected to assay TNF-α, IL-6, renin and angiotensinogen mRNA levels. After a 4-h intravenous infusion of Ang II, renal TNF-α or IL-6 mRNA level significantly increased 1.9-fold or 2.1-fold (each P<0.05) to the control level, respectively. LPS stimulated TNF-α, IL-6 and angiotensinogen mRNA levels in the kidney but in rats given enalapril or TCV-116, LPS-induced IL-6 and TNF-α mRNA levels were completely suppressed (each P<0.05). This suggests that a single dose of renin-angiotensin system inhibitor suppressed renal IL-6 and TNF-α production and may prevent cytokine-induced renal damage during endotoxemia.
社団法人日本薬理学会の論文
2002-02-01