Korean Journal of Nephrology 1999;18(1):52-62.

사구체 신염 환자들에게 말초혈액 단핵세포의 Cytokine들의 유전자 발현에 대한 ACE Inhibitor의 영향 (The Effect of ACE Inhibitors on the Gene Expression of Various Cytokines in Peripheral Blood Mononuclear Cells from Patients with Glomerular Diseases : TGF-β, IL-6, IL-10 and TNF-α)

김승정, 신규태, 마경애, 김상돈, 이한민, 지석배, 김홍수, 김도헌 (Seung Jung Kim, Gyu Tae Shin, Kyoung Ai Ma, Sang Don Kim, Han Min Lee, Seog Bae Ji, Heung Soo Kim, Do Hun Kim and )

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-β1, IL-6, TNF-α and IL-10. The ratios of target cytokines and β-actin were calculated. TGF-β1 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-α 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-β1 in PBMC suggests that the in vivo attenuating effect of ACE inhibitors on TGF-β1 may be derived from renal hemodynamic changes. The tendency of heightened expression of TNF-α confirms the previous investigations in which IL-6 was shown to down regulate TNF-α expression