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CLINICAL STUDY: CARDIOMYOPATHY

Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy

^a Second Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan

Manuscript received June 5, 2000; revised manuscript received August 23, 2000, accepted October 3, 2000.

Reprint requests and correspondence: Dr. Tomoaki Ohtsuka, Second Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan
mhamada{at}m.ehime-u.ac.jp

OBJECTIVES

This study was designed to evaluate the beneficial effect of beta-blockers on circulating cytokine levels in patients with dilated cardiomyopathy (DCM).

BACKGROUND

Elevated circulating levels of inflammatory cytokines have been reported in patients with DCM. However, alterations of the levels of inflammatory and anti-inflammatory cytokines in association with beta-blocker therapy are unknown.

METHODS

We studied 32 patients with idiopathic DCM who had been treated with digitalis, diuretics and angiotensin-converting enzyme inhibitors. In addition to this combination therapy, beta-blockers were started in all patients. Serum levels of interleukin (IL)-10, tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNF-R1 and R2) were measured at baseline and 12 weeks after the initiation of beta-blocker therapy. We also measured plasma levels of neurohumoral factors, as well as left ventricular (LV) size and function. Ten age-matched subjects with no cardiac disease served as the control group.

RESULTS

Baseline levels of IL-10, TNF-alpha and sTNF-R2 were significantly higher in patients with DCM than in control subjects (p < 0.05). There was a significant positive correlation between IL-10 and TNF-alpha levels (r = 0.545, p = 0.029). The TNF-alpha/IL-10 ratio correlated well with plasma epinephrine levels (r = 0.677, p = 0.025), and the level of sTNF-R2 was closely related to LV size. Serum levels of IL-10, TNF-alpha and sTNF-R2 were significantly decreased during beta-blocker therapy (p < 0.005).

CONCLUSIONS

Our findings indicate that beta-blockers have an important immunoregulatory role in modifying the dysregulated cytokine network in DCM. This effect of beta-blockers may be partly responsible for the efficacy of therapeutic drugs for heart failure.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   CHF = congestive heart failure   DCM = dilated cardiomyopathy   EDD = end-diastolic dimension   ESD = end-systolic dimension   IL = interleukin   LV = left ventricular   sTNF-R = soluble tumor necrosis factor receptor   TNF-alpha = tumor necrosis factor-alpha

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