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CLINICAL STUDIES

Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure

^a First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Japan

Manuscript received May 28, 1999; revised manuscript received October 5, 1999, accepted November 15, 1999.

Reprint requests and correspondence: Takayoshi Tsutamoto, First Department of Internal Medicine, Shiga University of Medical Science Tsukinowa, Seta, Otsu 520-2192, Japan.
tutamoto{at}belle.shiga-med.ac.jp

OBJECTIVES

To evaluate the effects of an angiotensin (Ang II) type 1 receptor antagonist on immune markers in patients with congestive heart failure (CHF).

BACKGROUND

Ang II stimulates production of immune factors via the Ang II type 1 receptor in vitro, and the long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation are unknown in patients with CHF.

METHODS

Twenty-three patients with mild to moderate CHF with left ventricular dysfunction were randomly divided into two groups: treatment with Ang II type 1 receptor (candesartan cilexetil) (n = 14) or placebo (n = 9). We measured plasma levels of immune factors such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). We also measured plasma levels of the neurohumoral factors such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP), a biological marker of ANP and BNP.

RESULTS

Plasma levels of TNFalpha, IL-6, sICAM-1 and sVCAM-1 were increased in the 23 CHF patients compared with normal subjects and significantly decreased after 14 weeks of candesartan cilexetil treatment, but did not change in the placebo group. Plasma levels of BNP, which is a marker of ventricular injury, significantly decreased, and the molar ratio of plasma cGMP to cardiac natriuretic peptides (ANP + BNP) was significantly increased after candesartan cilexetil treatment, but did not change in the placebo group.

CONCLUSIONS

These findings suggest that 14 weeks of treatment with an Ang II type 1 receptor antagonist (candesartan cilexetil) decreased plasma levels of the immune markers such as TNFalpha, IL-6, sICAM-1 and sVCAM-1 and that it improved the biological compensatory action of endogenous cardiac natriuretic peptides in patients with mild to moderate CHF.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ALD = aldosterone   Ang II = angiotensin II   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   cGMP = cyclic guanosine monophosphate   CHF = congestive heart failure   ET-1 = endothelin-1   ICAM-1 = intercellular adhesion molecule-1   IL-6 = interleukin-6   LVEF = left ventricular ejection fraction   NE = norepinephrine   NYHA = New York Heart Association   PARC = plasma active renin concentration   sICAM-1 = soluble intercellular adhesion molecule-1   sVCAM-1 = soluble vascular adhesion molecule-1   TNFalpha = tumor necrosis factor alpha   VCAM-1 = vascular cell adhesion molecule-1

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