Cytokine production and lymphocyte subpopulations in aged humans. An assessment during nocturnal sleep

The view of a general impairment of immune functions associated with aging has been challenged by recent studies including a more detailed evaluation of various cytokines and lymphocyte subsets. In the present human study, effects of age on the production of cytokines by T cells and monocytes were assessed, together with age-dependent changes in subset populations of mononuclear cells (MNC). Blood was collected every 30 min during nocturnal sleep in 16 aged (mean: 79.6 +/- 7.5 years) and in 16 young controls (mean: 24.6 +/- 3.1 years). Nocturnal sleep was chosen as a well-defined period within the 24-h cycle with minimal exogenous influences. The in vitro production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) was measured after mitogen stimulation with lipopolysaccharide from E. coli (LPS). Production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) was measured after stimulation with phytohemagglutinin (PHA). Regarding MNC subsets, monocytes, lymphocytes, CD3(+), CD4(+), CD8(+), HLA-DR, CD16(+), CD25(+), and CD19(+) were determined. Advanced age was associated with a decreased number of T cells (CD3 +) and decreases in the major T cell subsets (CD4(+), CD8(+), P < 0.001). Production of IL-2 was not affected. However, production of IFN-gamma tended to be enhanced, and numbers of activated T cells (HLA-DR/CD3(+)), natural killer cells (CD16(+)), and T cells expressing IL-2 receptors (CD25(+)/CD3(+)) were markedly increased in the aged. While monocyte counts were unchanged in the elderly production of IL-1 beta and TNF-alpha mainly derived from these cells, was enhanced (p < 0.05). Results indicate a state of enhanced responsiveness of the T cell compartment and of monocytes in aged which may compensate for the substantial decrease in T cells.