The relationship between age and production of tumour necrosis factor-α in healthy volunteers and patients with chronic heart failure

Background: Ageing is associated with an altered immune response. Elevated plasma levels of tumour necrosis factor-α (TNF-α) are present in patients with advanced chronic heart failure (CHF). However, the relationship between age and the immune response in CHF is unknown. Methods: We investigated the relationship between age and the TNF-α generating capacity of lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in nine healthy control subjects (mean age 51.6±3.6 years, age range 39–75 years) and 22 stable patients with CHF (mean age 68.3±1.5 years, age range 52–78 years, NYHA class 3.0±0.2). We also tested the TNF-α generating capacity of all control subjects and 18 CHF patients in whole blood cultures. Results: Subjects were subgrouped according to baseline TNF-α secretion in PBMC cultures into low- and high-responders, with the latter producing TNF-α even without LPS stimulation. High-responders produced more TNF-α than low-responders at all LPS doses (0.001–10 ng/ml, P<0.0001, repeated measures ANOVA), and high-responders were significantly older than low-responders (controls: 65.8±9.2 vs. 47.5±2.5 years; patients: 71.9±1.9 vs. 65.9±1.9 years, both P<0.05). Age correlated with TNF-α production in both patients and controls. This effect was independent of NYHA class. Conclusions: LPS-responsiveness appears to relate to age in both healthy controls and CHF patients. When assessing the immune status of CHF patients, age should therefore be considered an important confounding factor. In whole blood these findings could only be confirmed at the highest LPS concentration used, thus suggesting that certain factors in the blood may be able to abolish LPS activity at lower concentrations.