title: Adverse environmental conditions influence age-related innate immune responsiveness.
abstract: BACKGROUND
  The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions.
  
  
  METHODS
  We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20-68 years old, n = 304) and a population living under adverse environmental conditions in Ghana (age 23-95 years old, n = 562).
  
  
  RESULTS
  We found a significant decrease in LPS-induced Interleukin (IL)-10 and Tumor Necrosis Factor (TNF) production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan.
  
  
  CONCLUSIONS
  We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands. l.may@lumc.nl
authors.forename: Linda
authors.initials: L
authors.lastname: May
authors.forename: Anita H J
authors.initials: AH
authors.lastname: van den Biggelaar
authors.forename: David
authors.initials: D
authors.lastname: van Bodegom
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Meij
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Joseph
authors.initials: J
authors.lastname: Amankwa
authors.forename: Marijke
authors.initials: M
authors.lastname: Frölich
authors.forename: Maris
authors.initials: M
authors.lastname: Kuningas
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp