title: Cytokine release from alveolar macrophages exposed to ambient particulate matter: heterogeneity in relation to size, city and season.
abstract: BACKGROUND
  Several studies have demonstrated an association between exposure to ambient particulate matter (PM) and respiratory and cardiovascular diseases. Inflammation seems to play an important role in the observed health effects. However, the predominant particle component(s) that drives the inflammation is still not fully clarified. In this study representative coarse (2.5-10 microm) and fine (0.1-2.5 microm) particulate samples from a western, an eastern, a northern and a southern European city (Amsterdam, Lodz, Oslo and Rome) were collected during three seasons (spring, summer and winter). All fractions were investigated with respect to cytokine-inducing potential in primary macrophages isolated from rat lung. The results were related to the physical and chemical parameters of the samples in order to disclose possible connections between inflammatory potential and specific characteristics of the particles.
  
  
  RESULTS
  Compared on a gram-by gram basis, both site-specific and seasonal variations in the PM-induced cytokine responses were demonstrated. The samples collected in the eastern (Lodz) and southern (Rome) cities appeared to be the most potent. Seasonal variation was most obvious with the samples from Lodz, with the highest responses induced by the spring and summer samples. The site-specific or seasonal variation in cytokine release could not be attributed to variations in any of the chemical parameters. Coarse fractions from all cities were more potent to induce the inflammatory cytokines interleukin-6 and tumour necrosis factor-alpha than the corresponding fine fractions. Higher levels of specific elements such as iron and copper, some polycyclic aromatic hydrocarbons (PAHs) and endotoxin/lipopolysaccaride seemed to be prevalent in the coarse fractions. However, variations in the content of these components did not reflect the variation in cytokine release induced by the different coarse fractions. Addition of polymyxin B did not affect the particle-induced cytokine release, indicating that the variations in potency among the coarse fractions are not explained by endootoxin.
  
  
  CONCLUSIONS
  The inflammatory potential of ambient PM demonstrated heterogeneity in relation to city and season. The coarse particle fractions were consistently more potent than the respective fine fractions. Though a higher level of some elements, PAH and endotoxin was found in the coarse fractions, the presence of specific components was not sufficient to explain all variations in PM-induced cytokine release.
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, N-0403 Oslo, Norway. ragna.hetland@fhi.no
authors.forename: Ragna B
authors.initials: RB
authors.lastname: Hetland
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
authors.forename: Marit
authors.initials: M
authors.lastname: Låg
authors.forename: Magne
authors.initials: M
authors.lastname: Refsnes
authors.forename: Erik
authors.initials: E
authors.lastname: Dybing
authors.forename: Per E
authors.initials: PE
authors.lastname: Schwarze