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(Chest. 2001;120:453-459.)
© 2001 American College of Chest Physicians

Effects of Vesnarinone on Peripheral Circulating Levels of Cytokines and Cytokine Receptors in Patients With Heart Failure*

A Report From the Vesnarinone Trial

Anita Deswal, MD; Nancy J. Petersen, PhD; Arthur M. Feldman, MD, PhD; Bill G. White, PhD and Douglas L. Mann, MD, FCCP

* From the Winters Center for Heart Failure Research, Houston VA Medical Center, Cardiology Section (Drs. Deswal and Mann), Department of Medicine, and Veterans Affairs Health Services Research and Development Center of Excellence (Dr. Petersen), Baylor College of Medicine, Houston, TX; Cardiovascular Institute of the University of Pittsburgh (Dr. Feldman), Medical Health System, Pittsburgh, PA; and Clinical Cardiovascular Research (Dr. White), Gaithersburg, MD.

Correspondence to: Douglas L. Mann, MD, FCCP, Cardiology Research (151C), Houston Veterans Affairs Medical Center, 2002 Holcombe Blvd, Houston, TX 77030; e-mail: dmann{at}bcm.tmc.edu

Study objectives: Proinflammatory cytokines may contribute to disease progression in heart failure by virtue of the direct toxic effects that these molecules exert on the heart and the circulation. Accordingly, there is interest in developing therapeutic agents with anticytokine properties that might be used as adjunctive therapy to modulate proinflammatory cytokine levels in patients with heart failure. Previous experimental studies suggested that vesnarinone has potent anticytokine properties in vitro. Therefore, we examined the effects of vesnarinone on circulating levels of cytokines and cytokine receptors in a large-scale, multicenter, clinical trial of patients with moderate-to-advanced heart failure: the Vesnarinone Trial (VEST).

Methods: Circulating levels of tumor necrosis factor (TNF)-{alpha}, soluble TNF-receptor type 1, soluble TNF-receptor type 2, as well as interleukin (IL)-6 and soluble IL-6 receptor (sIL-6R) were measured on plasma samples by enzyme-linked immunosorbent assay at baseline and at 24 weeks in patients who were receiving placebo (n = 352), 30 mg of vesnarinone (n = 367), and 60 mg of vesnarinone (n = 327).

Results: Treatment with 30 mg and 60 mg of vesnarinone had no effect on circulating levels of cytokines or cytokine receptors in patients with advanced heart failure over a 24-week period.

Conclusions: In contrast to the potent anticytokine effects observed with vesnarinone in experimental studies in vitro, the results of this clinical study suggest that vesnarinone does not have any measurable anticytokine effects in vivo in patients with moderate-to-advanced heart failure.

Key Words: cytokine • heart failure • interleukin-6 • receptor • soluble interleukin-6 receptor • soluble tumor necrosis factor-receptor type 1 • soluble tumor necrosis factor-receptor type 2 • tumor necrosis factor-{alpha} • vesnarinone






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