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

Ziad Dibbs, MD^* , John Thornby, PhD^* , B. G. White, PhD and Douglas L. Mann, MD, FACC^*

^* Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center, USA
Baylor College of Medicine, Houston, Texas, USA
Clinical Cardiovascular Research, LLC, Gaithersburg, Maryland, USA

View larger version (16K): [in a new window]   Figure 1 Circulating levels of tumor necrosis factor-alpha (TNF-) (A) and soluble TNF receptor type 1 (sTNFR1) (B) and type 2 (sTNFR2) (C) in heart failure (HF) and control subjects. To determine whether circulating levels of cytokine and cytokine receptors increased over time, the mean levels of TNF-, sTNFR1 and sTNFR2 were determined on a monthly basis for a period of 4 months (see Methods for details). Heart failure patients are depicted by solid squares, and healthy control subjects are depicted by open squares.

View larger version (18K): [in a new window]   Figure 2 Circulating levels of interleukin-6 (IL-6) (A) and soluble IL-6 receptor (sIL-6R) (B) in heart failure (HF) and control subjects. To determine whether circulating levels of cytokine and cytokine receptors increased over time, the mean levels of IL-6 and sIL-6R were determined on a monthly basis for a period of 4 months (see Methods for details). Heart failure patients are depicted by solid squares, and healthy control subjects are depicted by open squares.

View larger version (19K): [in a new window]   Figure 3 Variability in circulating tumor necrosis factor-alpha (TNF-) levels in heart failure and control subjects. The degree of TNF- variability was assessed by determining the coefficient of variation (CV) (see Methods) for daily, weekly and monthly TNF- levels. Each data point shown reflects the CV for a given subject. Heart failure patients are depicted by closed diamonds, and healthy control subjects are depicted by open squares. The mean ± SEM of the CVs in each group are shown to the right of each scatter plot. * = p < 0.05 compared with control subjects.

View larger version (16K): [in a new window]   Figure 4 Variability in circulating interleukin-6 (IL-6) levels in heart failure and control subjects. The degree of IL-6 variability was assessed by determining the coefficient of variation (CV) (see Methods) for daily, weekly and monthly IL-6 levels. Each data point shown reflects the CV for a given subject. Heart failure patients are depicted by closed diamonds, and healthy control subjects are depicted by open squares. The mean ± SEM of the CVs in each group are shown to the right of each scatter plot. * = p < 0.05 compared with control subjects.