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

J Am Coll Cardiol. 2001 Feb;37(2):412-7. doi: 10.1016/s0735-1097(00)01121-9.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Bisoprolol / therapeutic use*
  • Cardiomyopathy, Dilated / drug therapy*
  • Cardiomyopathy, Dilated / immunology
  • Cytokines / antagonists & inhibitors*
  • Cytokines / blood*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / blood*
  • Male
  • Metoprolol / therapeutic use*
  • Middle Aged
  • Treatment Outcome
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / immunology


  • Adrenergic beta-Antagonists
  • Cytokines
  • Inflammation Mediators
  • Metoprolol
  • Bisoprolol