Korean J Nephrol.  1999 Jan;18(1):52-62.

The Effect of ACE Inhibitors on the Gene Expression of Various Cytokines in Peripheral Blood Mononuclear Cells from Patients with Glomerular Diseases: TGF-beta, IL-6, IL-10 and TNF-alpha

• Kim SJ
• Shin GT
• Ma KA
• Kim SD
• Lee HM
• Ji SB
• Kim HS
• Kim DH

Abstract

Angiotensin II(ANG II) has been known to induce systemic and glomerular hypertension, which leads to renal tissue injury and progressive fibrosis of kidney. Some effects of ANG II may be mediated by its effect on the cytokine synthesis. In the present study, we investigated the effect of ANG II inhibition on the expression of various cytokines implicated in the pathogenesis and progression of the kidney disease. Blood samples of 11 patients with glomerulonephritis were obtained before the ACE inhibitor therapy and then while they were taking ACE inhibitors. Using peripheral blood mononuclear cells(PBMC) harvested from the samples, RT-PCR was performed to evaluate the changes in mRNA expression of TGF-beta1, IL-6, TNF-alpha and IL-10. The ratios of target cytokines and beta-actin were calculated. TGF-beta1 mRNA expression was decreased in five pat ients after ANG II inhibition with ACE inhibitors, while it was increased in the remaining six patients. ACE inhibitors consistently decreased IL-6 mRNA expression in all 11 patients. IL-10 expression was decreased in 4 patients, and increased in 3 patients after ANG II inhibition. It was not expressed in 4 patients. TNF-alpha expression was increased in 8 patients, and decreased in only 1 patient. In two patients, it was not changed while on ACE inhibitors.
Conclusion
ACE inhibitors attenuate IL-6 expression consistently in all 11 patients. This is the first-time demonstration of the in vivo inhibitory effect of ACE inhibitors on IL-6 mRNA expression in humans. The lack of significant suppression of TGF-beta1 in PBMC suggests that the in vivo attenuating effect of ACE inhibitors on TGF-beta1 may be derived from renal hemodynamic changes. The tendency of heightened expression of TNF-alpha confirms the previous investigations in which IL-6 was shown to down regulate TNF-alpha expression

Keyword

Angiotensin II; ACE inhibitor; TGF-beta; IL-6; IL-10; TNF-alpha

MeSH Terms

Actins
Angiotensin II
Angiotensin-Converting Enzyme Inhibitors*
Angiotensins
Cytokines*
Fibrosis
Gene Expression*
Glomerulonephritis
Hemodynamics
Humans
Hypertension
Interleukin-10*
Interleukin-6*
Kidney
Kidney Diseases
RNA, Messenger
Transforming Growth Factor beta*
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha*
Actins
Angiotensin II
Angiotensin-Converting Enzyme Inhibitors
Angiotensins
Cytokines
Interleukin-10
Interleukin-6
RNA, Messenger
Transforming Growth Factor beta
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha