CYTOKINE PRODUCTION BY HUMAN AIRWAY EPITHELIAL-CELLS AFTER EXPOSURE TO AN AIR-POLLUTION PARTICLE IS METAL-DEPENDENT

Despite the many epidemiological studies supporting the contention tha t ambient air pollution particles can adversely affect human health, t here is no clear agreement as to a biologically plausible mechanism wh ich can explain the acute mortality and morbidity associated with expo sure to particles less than 10 mu m in size. We tested the hypothesis that metals present in an air pollution particle can induce the synthe sis and expression of the inflammatory cytokines IL-8, IL-6, and TNF a lpha. A residual oil fly ash (ROFA) containing the transition metals v anadium, nickel, and iron was used as a model emission source air poll ution particle. Normal human bronchial epithelial (NHBE) cells were ex posed for either 2 or 24 hr to 0, 5, 50, or 200 mu g/ml ROFA. Concentr ations of IL-8, IL-6, and TNF-alpha proteins were measured with commer cially available ELISA kits. mRNA for these same cytokines was quantif ied by RT-PCR. NHBE cells exposed to ROFA produced significant amounts of IL-8, IL-6, and TNF, as well as mRNAs coding for these cytokines. Cytokine production was inhibited by the inclusion of either the metal chelator deferoxamine (1.0 mM) or the free radical scavenger dimethyl thiourea (1.0 mM). In addition, vanadium containing compounds, but not iron or nickel sulfates, mimicked the effects of intact ROFA. These r esults demonstrate that metals present in ROFA may be responsible for production and release of inflammatory mediators by the respiratory tr act epithelium and suggest that these mediators may contribute to the toxic effects of particulate air pollutants reported in epidemiology s tudies. (C) 1997 Academic Press.