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 cardiac tissue when overexpressed in human subjects. Previous studies have shown that levels of circulating TNF-alpha are elevated in patients with advanced congestive heart failure (CHF) and especially in those with cardiac cachexia. To clarify the potential role of TNF-alpha in the unstable state of decompensated advanced CHF, we investigated the TNF-alpha serum activity in 25 cachectic and 22 non-cachectic CHF patients (New York Heart Association, NYHA functional classes III or IV), who were treated with intravenous diuretics and positive inotropic agents for acute decompensation of the disease, during a 5-day hospitalization period, as well as in 15 age-matched healthy control subjects. Cachectic CHF patients needed higher dosages of inotropic 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 circulating TNF-alpha during the treatment period with the highest levels on the 2nd day of hospitalization (32.5 +/- 7.1 pg/ml). The TNF-alpha serum levels were low in non-cachectic CHF patients and healthy controls on the 1st day (4.0 +/- 0.9 and 3.7 +/- 0.6 pg/ml, respectively) and did not change substantially during the course of the study. The present results show that TNF-alpha serum activity is transiently increased during the treatment of decompensated cachectic CHF patients only and may be related to the clinical instability and the consequent therapeutic interventions in this category of CHF patients.

Correlation of interleukin-6 gene expression to immunologic features in patients with cardiac myxomas.

Cardiac myxomas, the most common primary heart tumors in adults, show a variety of clinical manifestations and laboratory findings correlated with elevated interleukin-6 (IL-6) serum concentration. The aim of this study was to determine the expression of IL-6 mRNA in myxoma tissue as a cause to frequent immunologic abnormalities in patients with such tumors. In our centers, we analyzed 17 surgically resected myxomas using the polymerase chain reaction (PCR) and found increased IL-6 mRNA expression in 14 of 17 cases. The serum IL-6 levels of the 14 patients, detected by enzyme-linked immunosorbent assay (ELISA) with mouse antihuman monoclonal antibody (mAb), were high preoperatively (> 6 pg/ml) and decreased to normal postoperatively (< or = 6 pg/ml). These same 14 patients exhibited significant autoimmune disorders preoperatively. The other 3 patients had normal serum levels of IL-6 (< or = 6 pg/ml) and did not present any serious signs and symptoms, and molecular analysis did not show overexpression of IL-6 mRNA in neoplasmic tissue. These results suggest that IL-6 is overproduced in myxoma tissue and secreted into the systemic circulation as a stimulator of the immunoregulatory system. Furthermore, this study indicates the promising role of molecular biology techniques in the research of pathophysiologic mechanisms of cardiac myxomas.