The relationship between age and production of tumour necrosis factor-alpha 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-alpha (TNF-alpha) 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-alpha 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-alpha generating capacity of all control subjects and 18 CHF patients in whole blood cultures.


RESULTS
Subjects were subgrouped according to baseline TNF-alpha secretion in PBMC cultures into low- and high-responders, with the latter producing TNF-alpha even without LPS stimulation. High-responders produced more TNF-alpha 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-alpha 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.
von Haehling
Stephan
S
Department of Clinical Cardiology, National Heart and Lung Institute, London SW3 6LY, UK. stephan.von.haehling@web.de
Genth-Zotz
Sabine
S
Sharma
Rakesh
R
Bolger
Aidan P
AP
Doehner
Wolfram
W
Barnes
Peter J
PJ
Coats
Andrew J S
AJ
Anker
Stefan D
SD
D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D008070:Lipopolysaccharides / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha