title: High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes.
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)-alpha are strongly associated with morbidity and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-alpha levels are unknown.
  
  
  OBJECTIVE
  The aim of the present study was to investigate if high plasma levels of TNF-alpha are associated with increased production of TNF-alpha by T lymphocytes in elderly humans.
  
  
  METHODS
  TNF-alpha 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-alpha increased with increasing age. An increased percentage and number of T lymphocytes from the 81 year olds expressed TNF-alpha, whereas centenarians did not show this altered TNF-alpha secretion profile.
  
  
  CONCLUSIONS
  T cells may contribute to the elevated levels of plasma TNF-alpha in healthy elderly subjects, whereas other mechanisms are responsible in very old individuals.
authors.affiliation: The Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Sandmand
authors.forename: Helle
authors.initials: H
authors.lastname: Bruunsgaard
authors.forename: Kåre
authors.initials: K
authors.lastname: Kemp
authors.forename: Karen
authors.initials: K
authors.lastname: Andersen-Ranberg
authors.forename: Marianne
authors.initials: M
authors.lastname: Schroll
authors.forename: Bernard
authors.initials: B
authors.lastname: Jeune
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over / Q000502:physiology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D014409:Tumor Necrosis Factor-alpha