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-α) plays an important role in the pathogenesis of congestive heart failure and that drugs used in the treatment of heart failure have modulation effects on the production of TNF-α. To examine an alteration of circulating TNF-α concentration in patients with severe chronic heart failure after improving heart function and investigate the influence of agents on circulating TNF-α concentrations, we measured the plasma levels of TNF-α by enzyme linked immunoabsorbent assay in 31 patients and evaluated their heart functions before and after 72 h of therapy. The results showed that circulating TNF-α 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-α concentrations of patients (n=22) whose heart function was improved one class 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 patients (n=9) whose heart functions had no or little improvement. All patients were divided into three groups according to their management: ‘group Aʹ (n=14) who received milrinone and angiotensin-converting enzyme inhibitors (ACEI), ‘group Bʹ (n=6) who received milrinone but not ACEI and ‘group Cʹ (n=11) who received ACEI and dobutamine but not milrinone. The circulating TNF-α concentration of patients in group A significantly declined (from 126.68±26.04 pg/ml to 95.92±24.79 pg/ml, P<0.01). No statistical significance of change of TNF-α 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-α level accompanies the improvement of heart function. This phenomenon may be explained by the special abilities of agents, such as ACEI and milrinone, to inhibit the TNF-α production.