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Eplerenone inhibits tumour necrosis factor α shedding process by tumour necrosis factor α converting enzyme in monocytes from patients with congestive heart failure
  1. M Satoh,
  2. Y Ishikawa,
  3. Y Minami,
  4. T Akatsu,
  5. M Nakamura
  1. Second Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan
  1. Correspondence to:
    Dr Mamoru Satoh
    Second Department of Internal Medicine, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan; m_satoh{at}imu.ncvc.go.jp

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Eplerenone, a selective mineralocorticoid receptor antagonist, attenuated the expression of systemic proinflammatory molecules in a rat model of congestive heart failure (CHF).1 However, the mechanisms by which eplerenone reduces proinflammatory molecule expression have not been elucidated. Our previous study was the first to show that expression of tumour necrosis factor α (TNFα) converting enzyme (TACE) in peripheral blood mononuclear cells may be responsible for the release of TNFα in CHF.2 To the best of our knowledge, the observation that peripheral monocytes can activate the TACE–TNFα system in CHF is without precedent. The objective of the present study was to examine whether monocytes have a role in the activated TACE–TNFα system and to determine whether eplerenone reduces the TNFα shedding process in monocytes from patients with CHF.

METHODS

Peripheral monocytes were isolated from blood samples at the time of admission (32 patients with CHF and 10 healthy subjects). The origin of left ventricular (LV) dysfunction was idiopathic dilated cardiomyopathy in all cases. Echocardiography …

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