Leukocyte Redistribution: Effects of Beta Blockers in Patients with Chronic Heart Failure

Background: Overproduction of pro-inflammatory cytokines is a well established factor in the progression of chronic heart failure (CHF). Changes in cellular immunity have not been widely studied, and the impact of standard medication is uncertain. Here we investigate whether a leukocyte redistribution occurs in CHF and whether this effect is influenced by beta-blocker therapy. Methodology: We prospectively studied 75 patients with systolic CHF (age: 68 +/- 11 years, left ventricular ejection fraction 32 +/- 11%, New York Heart Association class 2.5 +/- 0.7) and 20 age-matched healthy control subjects ( age: 63 +/- 10 years). We measured the response of cells to endotoxin exposure in vitro, analysed subsets of lymphocytes using flow cytometry, and assessed plasma levels of the pro-inflammatory markers interleukin 1, 6, tumor necrosis factor-alpha, and soluble tumor necrosis factor receptors 1 and 2. Principal findings: While no differences in the number of leukocytes were noted between patients with CHF and healthy controls, we detected relative lymphopenia in patients with CHF (p < 0.001 vs. control), mostly driven by reductions in T helper cells and B cells (both p < 0.05). The number of neutrophils was increased (p < 0.01). These effects were pronounced in patients who were beta-blocker naive (32% of all patients with CHF). Increased plasma levels of soluble tumor necrosis receptor-1 correlated with the relative number of lymphocyte subsets. Conclusions: In patients with CHF, we detected a redistribution of leukocyte subsets, i.e. an increase in neutrophils with relative lymphopenia. These effects were pronounced in patients who were beta-blocker naive. The underlying mechanism remains to be elucidated.