Effects of vesnarinone on peripheral circulating levels of cytokines and cytokine receptors in patients with heart failure: a report from the Vesnarinone Trial.
OBJECTIVE
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.
Deswal
A
A
Winters Center for Heart Failure Research, Houston VA Medical Center, Cardiology Section, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Petersen
N J
NJ
Feldman
A M
AM
White
B G
BG
Mann
D L
DL
D002316:Cardiotonic Agents / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D018121:Receptors, Cytokine / Q000097:blood*; D019947:Receptors, Interleukin-6 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D002316:Cardiotonic Agents; D016207:Cytokines; D015850:Interleukin-6; D011719:Pyrazines; D011804:Quinolines; D018121:Receptors, Cytokine; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C041667:vesnarinone