PROINFLAMMATORY CYTOKINE LEVELS IN PATIENTS WITH DEPRESSED LEFT-VENTRICULAR EJECTION FRACTION - A REPORT FROM THE STUDIES OF LEFT-VENTRICULAR DYSFUNCTION (SOLVD)

Objectives. This study Sought to assess proinflammatory cytokine level s in patients in the studies of left ventricular dysfunction trial (SO LVD) in relation to both their New York Heart Association functional c lassification and their neurohormonal status before randomization. Bac kground. Elevated levels of tumor necrosis factor-alpha have been iden tified in 30% to 40% of patients with heart failure. However, it is un clear wi;ich subsets of patients with heart failure elaborate tumor ne crosis factor-alpha. It is also unclear what the mechanism for the inc reased expression of proinflammatory cytokines is. Methods. Tumor necr osis factor-alpha and interleukin-6 levels were analyzed by enzyme lin ked immunoassay using randomly selected plasma samples from patients i n functional classes I to III who were enrolled in neurohormonal subst udies of the SOLVD trial; age-matched healthy Subjects served as the c ontrol group.Results. Plasma levels. of tumor necrosis factor-alpha (p < 0.001) were elevated in patients in functional classes I to III ([m ean +/- SD] 1.95 +/- 0.54, 2.63 +/- 0.48, 6.4 +/- 1.9 pg/ml, respectiv ely) compared with age-matched control subjects (0.75 +/- 0.05 pg/ml) and were progressively elevated in relation to decreasing functional s tatus of the patient. Plasma levels of interleukin-6 (p < 0.001) were elevated in patients in functional classes I to III (3.3 +/- 0.55, 6.2 +/- 1.1, 5.22 +/- 0.9 pg/ml, respectively) compared with age-matched control subjects (1.8 +/- 0.5 pg/ml) and were progressively elevated i n relation to decreasing functional status of the patient. Cox proport ional-hazards analysis showed that there was a trend toward significan ce between plasma tumor necrosis factor-alpha (p < 0.07) and survival, whereas there was no significant relation for plasma interleukin-6 (p < 0.72). Except for atrial natriuretic factor, which correlated weakl y (r = 0.23, p = 0.04) with circulating tumor necrosis factor-alpha le vels, there was no significant correlation between neurohormonal and p roinflammatory cytokine levels. Conclusions. Circulating levels of pro inflammatory cytokines increase in patients as their functional heart failure classification deteriorates. Moreover, activation of the neuro humoral axis is unlikely to completely explain the elaboration of proi nflammatory cytokines in heart failure.