The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-␣), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-␣ and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.It has been suggested that there exists an age-related defective acute-phase response (11). This is supported by reports of afebrile bacteremia in elderly patients (10). In other studies, lack of fever and of leukocytosis were associated with a poor outcome of community-acquired pneumonia (15) and elderly patients had decreased levels of inflammatory cytokines in plasma in the acute phase compared to those in young patients (11). The purpose of the present study was to examine if the acute-phase response in a human sepsis model differed between old and young individuals.It is possible that gram-positive and gram-negative bacteria may induce different patterns of cytokine response. However, the only experimental sepsis model currently established in humans is the endotoxin model (6). We therefore applied this model to groups of healthy young people and of healthy elderly people. In this model, a standard reference Escherichia coli endotoxin is injected (2 to 4 ng/kg). We chose a dose of 2 ng/kg taking into account the fact that elderly individuals may not tolerate the same dosages as young subjects. As an expression of the acute-phase response, we measured changes in concentrations of a series of cytokines, including tumor necrosis factor alpha (TNF-␣), interleukin-6 (IL-6), soluble TNF receptors (sTNFR-I), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra), as well as C-reactive protein (CRP), in plasma. We also measured changes in body temperature.
MATERIALS AND METHODSVolunteers. Eight healthy young volunteers (five men, three women) with a median age of 24 years (range, 20 to 27 years) were compared to a group of nine healthy eld...