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 i nteractions between the sympathetic nervous system and the immune system. W e 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 place bo in a double-blind trial. Plasma levels of tumor necrosis factor (TNF)-al pha, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), monocyte ch emoattractant 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 III at baseline TNF-alpha, IL-6, IL-8, monoc yte chemoattractant peptide-l,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 throug hout the study in both the metoprolol and the placebo groups. Conclusions our findings suggest that metoprolol treatment in CHF is associ ated with a significant but temporary decrease in sIL-2R, possibly reflecti ng down-modulation of T-cell activation. However, an enhanced immune activa tion also persisted in the metoprolol group, suggesting a potential for mor e specific immunomodulatory therapy in CHF.