Interleukin-8 levels in human lung epithelial cells are increased in response to coal fly ash and vary with the bioavailability of iron, as a function of particle size and source of coal

Particulate air pollution contains iron, and some of the pathological effec ts after inhalation may be due to radical species produced by iron-catalyze d reactions. We tested the hypothesis that iron present in coal fly ash (CF A) could induce the expression and synthesis of the inflammatory cytokine i nterleukin-8 (IL-8). CFA, containing as much as 14% iron, was used as a mod el combustion source particle. Three coal types were used to generate three size fractions enriched in particles [submicron (<1 mu m), fine (<2.5 mu m ), or coarse (2.5-10 mu m)], as well as the fraction of >10 mu m. Treatment of human lung epithelial (A549) cells for 4 h with CFA from Utah enriched in <1 mu m particles (20 mu g/cm(2)) resulted in a 2.6-fold increase in mRN A levels for IL-8. IL-8 levels were increased in the medium by as much as 8 -fold when cells were treated with the fraction enriched in the smallest si ze Utah CFA for 24 h. IL-8 production was completely inhibited when the CFA was pretreated with the metal chelator desferrioxamine B, suggesting that a transition metal was responsible for the induction, probably iron. Treatm ent with a soluble form of iron, ferric ammonium citrate (FAC), mimicked th e IL-8 level increase observed with CFA. There was a direct relationship, a bove a threshold level of bioavailable iron, between the levels of IL-8 and bioavailable iron in A549 cells treated with CFA or FAC. Further, the rela tionship between IL-8 and bioavailable iron for CFA was indistinguishable f rom that for FAC. These results strongly suggest that iron can induce IL-8 in A549 cells and that iron was the likely component of CFA that induced IL -8. CFA-induced IL-8 production was inhibited by tetramethylthiourea or dim ethyl sulfoxide, suggesting that radical species were involved in the induc tion. These results demonstrate that iron present in CFA may be responsible for production and release of inflammatory mediators by the lung epitheliu m through generation of radical species and suggest that iron may contribut e to the exacerbation of respiratory problems by particulate air pollution.