Natural variability of circulating levels of cytokines and cytokine receptors in patients with heart failure: Implications for clinical trials

OBJECTIVES The purpose of this Emd,was to examine the variability in cytoki nes and cytokine receptor in patients with heart failure in comparison with a group of healthy control subjects who were free of cardiovascular diseas e. BACKGROUND Despite increasing interest in cytokine, as mediators of disease progression in heart failure and the recent interest in suppressing cytoki nes in clinical studies, the extent of variability in cytokines and cytokin e receptors is largely unknown This information is important for interpreti ng the results of studies in which changes in cytokine levels are measured in response to a specific form of therapy. METHODS Circulating levels of tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptors (types 1 and 2), as well as interleukin (IL)-6 and IL -6 receptor were measured on a daily, weekly and monthly basis in heart fai lure patients (New York Heart Association class IIIa and IIIb; n =. 10) and healthy volunteer subjects (n = 10). Measurements of cytokines and cytokin e receptors were performed on plasma samples by enzyme-linked immunoassay T he daily, weekly and monthly degree of variability in cytokine and cytokine receptor levels was assessed by determining the coefficient of variation e ach point in time. The coefficient of variation for TNF-alpha and IL-6 leve ls increased over time in patients with heart failure; moreover, the coeffi cient of variation in heart failure subjects was significantly greater for IL-6 than for TNF-alpha. RESULTS The coefficient of variation in n;cytokine receptor levels was mini mal, and did not differ significantly between heart failure and control sub jects free of cardiovascular disease. CONCLUSIONS In patients with heart failure the degree of natural variabilit y in circulating cytokine levels increases with time, and is greater for IL -6 than for TNF-alpha. Accordingly, the results of the present study sugges t that the sample size needed to show a statistically significant change in the circulating level of a given cytokine will vary depending on the speci fic cytokine that is being measured, as well as the time period over which that cytokine is being assayed. (C) 1999 by the American College.