Abstract
Background: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-α are strongly associated with morbidity and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-α levels are unknown. Objective: The aim of the present study was to investigate if high plasma levels of TNF-α are associated with increased production of TNF-α by T lymphocytes in elderly humans. Methods: TNF-α production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14 81-year-olds and 25 centenarians. Results: Plasma levels of TNF-α increased with increasing age. An increased percentage and number of T lymphocytes from the 81 year olds expressed TNF-α, whereas centenarians did not show this altered TNF-α secretion profile. Conclusion: T cells may contribute to the elevated levels of plasma TNF-α in healthy elderly subjects, whereas other mechanisms are responsible in very old individuals.