Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy.
OBJECTIVE
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.
Ohtsuka
T
T
Second Department of Internal Medicine, Ehime University School of Medicine, Japan. mhamada@m.ehime-u.ac.jp
Hamada
M
M
Hiasa
G
G
Sasaki
O
O
Suzuki
M
M
Hara
Y
Y
Shigematsu
Y
Y
Hiwada
K
K
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D017298:Bisoprolol / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000097:blood*; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects / Q000276:immunology
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D018836:Inflammation Mediators; D008790:Metoprolol; D017298:Bisoprolol