The changes of circulating tumor necrosis factor levels in patients with congestive heart failure influenced by therapy

Recent studies suggest that tumor necrosis factor-alpha (TNF-alpha) plays a n important role in the pathogenesis of congestive heart failure and that d rugs used in the treatment of heart failure have modulation effects on the production of TNF-alpha. To examine an alteration of circulating TNF-alpha concentration in patients with severe chronic heart failure after improving heart function and investigate the influence of agents on circulating TNF- alpha concentrations, we measured the plasma levels of TNF-alpha by enzyme linked immunoabsorbent assay in 31 patients and evaluated their heart funct ions before and after 72 h of therapy. The results showed that circulating TNF-alpha concentrations significantly decreased after therapy (from 124.36 +/-14.85 pg/ml to 93.84+/-13.57 pg/ml, P<0.001). The circulating TNF-alpha concentrations of patients (n=22) whose heart function was improved one cla ss or more after therapy declined significantly (from 127.51+/-20.78 pg/ml to 91.54+/-18.56 pg/ml, P<0.01) but this situation did not exist in patient s (n=9) whose heart functions had no or little improvement. All patients we re divided into three groups according to their management: 'group A' (n=14 ) who received milrinone and angiotensin-converting enzyme inhibitors (ACEI ), 'group B' (n=6) who received milrinone but not ACEI and 'group C' (n=11) who received ACEI and dobutamine but not milrinone. The circulating TNF-al pha concentration of patients in group A significantly declined (from 126.6 8+/-26.04 pg/ml to 95.92+/-24.79 pg/ml, P<0.01). No statistical significanc e of change of TNF-alpha concentration was found in patients in group B or group C, although a tendency of decline existed (from 119.92+/-34.72 pg/ml to 84.33+/-30.70 pg/ml and from 123.83+/-19.50 pg/ml to 96.37+/-16.62 pg/ml , respectively). These findings support that decreased plasma TNF-alpha lev el accompanies the improvement of heart function. This phenomenon may be ex plained by the special abilities of agents, such as ACEI and milrinone, to inhibit the TNF-alpha production. (C) 1999 Elsevier Science Ireland Ltd. Al l rights reserved.