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

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Abstract

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

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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