Tumor necrosis factor-alpha serum activity during treatment of acute decompensation of cachectic and non-cachectic patients with advanced congestive heart failure

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that produces left ventricular dysfunction and a negative inotropic effect in ca rdiac tissue when overexpressed in human subjects. Previous studies have sh own that levels of circulating TNF-alpha are elevated in patients with adva nced congestive heart failure (CHF) and especially in those with cardiac ca chexia. To clarify the potential role of TNF-alpha in the unstable state of decompensated advanced CHF, we investigated the TNF-alpha serum activity i n 25 cachectic and 22 non-cachectic CHF patients (New York Heart Associatio n, NYHA functional classes III or IV), who were treated with intravenous di uretics and positive inotropic agents for acute decompensation of the disea se, during a 5-day hospitalization period, as well as in 15 age-matched hea lthy control subjects. Cachectic CHF patients needed higher dosages of inot ropic agents than non-cachectic patients and the determination of TNF-alpha serum concentrations in this patient group showed high levels of TNF-alpha at hospital admission (18.3 +/- 3.2 pg/ml) and a transient increase in cir culating TNF-alpha during the treatment period with the highest levels on t he 2nd day of hospitalization (32.5 +/- 7.1 pg/ml). The TNF-alpha serum lev els were low in non-cachectic CHF patients and healthy controls on the Ist day (4.0 +/- 0.9 and 3.7 +/- 0.6 pg/ml, respectively) and did not change su bstantially during the course of the study. The present results show that T NF-alpha serum activity is transiently increased during the treatment of de compensated cachectic CHF patients only and may be related to the clinical instability and the consequent therapeutic interventions in this category o f CHF patients.