Effect of metoprolol on cytokine levels in chronic heart failure--a substudy in the Metoprolol Controlled-Release Randomised Intervention Trial in Heart Failure (MERIT-HF).
BACKGROUND
Enhanced immune activation has been suggested to be involved in the pathogenesis of congestive heart failure (CHF). There is evidence for interactions between the sympathetic nervous system and the immune system. We therefore examined the effect of the selective beta(1)-receptor blocker metoprolol on various immunologic variables in CHF.


METHODS
Eighty-one patients with CHF were randomized to metoprolol or placebo in a double-blind trial. Plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), monocyte chemoattractant peptide-1, and IL-8 were measured at baseline, after 3 months, and at the end of the study (11.4 +/- 0.4 months).


RESULTS
Our main findings were (1) at baseline TNF-alpha, IL-6, IL-8, monocyte chemoattractant peptide-1, and sIL-2R but not IL-10 levels were markedly elevated in patients with CHF compared with controls; (2) during treatment with metoprolol, but not with placebo, there was a significant decrease in sIL-2R after 3 months, with a return to baseline at the end of the study; and (3) levels of all other immunologic variables remained unchanged throughout the study in both the metoprolol and the placebo groups.


CONCLUSIONS
Our findings suggest that metoprolol treatment in CHF is associated with a significant but temporary decrease in sIL-2R, possibly reflecting down-modulation of T-cell activation. However, an enhanced immune activation also persisted in the metoprolol group, suggesting a potential for more specific immunomodulatory therapy in CHF.
Division of Heart and Lung Diseases, Department of Cardiology, Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway.
L
L
Gullestad
T
T
Ueland
A
A
Brunsvig
J
J
Kjekshus
S
S
Simonsen
S S
SS
Frøland
P
P
Aukrust
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007378:Interleukins / Q000032:analysis; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D008790:Metoprolol