OZONE-INDUCED MEDIATOR RELEASE FROM HUMAN BRONCHIAL EPITHELIAL-CELLS IN-VITRO AND THE INFLUENCE OF NEDOCROMIL SODIUM

Although animal and human studies have demonstrated that ozone inhalat ion leads to airway epithelial inflammation and damage, the underlying mechanisms are not fully understood. We cultured human bronchial epit helial cells as explant cultures and investigated the effect of 6 h of exposure to 0-500 parts per billion (ppb) O-3 with or without 10(-5) M nedocromil sodium on: 1) epithelial cell membrane integrity; and 2) release of inflammatory cytokines and soluble intercellular adhesion m olecule-1 (sICAM-1), as assessed by enzyme-linked immunosorbent assay (ELISA).O-3 exposure led to significant epithelial cell damage at conc entrations of 10-500 ppb O-3, as indicated by increased release of [Cr -51]-labelled sodium chromate. At concentrations of 10-100 ppb, O-3 in duced maximal release of interleukin-8 (IL-8), granulocyte/macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF- alpha) and sICAM-1, The IL-8 and GM-CSF release increased significantl y from 5.64+/-0.58 and 0.04+/-0.03 pg .mu g(-1) cellular protein, resp ectively, from control cells exposed to air, to 20.16+/-2.56 and 0.20/-0.04 pg .mu g(-1) cellular protein, respectively, from cells exposed to 50 ppb O-3. 10(-5) M nedocromil sodium significantly attenuated th e O-3-induced release of both IL-8 and GM-CSF (p<0.01). The TNF-alpha and sICAM-1 increases after exposure to 10-50 ppb O-3, were also abrog ated by treatment of the cells with 10(-5) M nedocromil sodium (p<0.05 ). Similarly, the antioxidant, glutathione, at concentrations of 400-6 00 mu M, significantly reduced the O-3-induced release of IL-8 (p<0.05 ). In conclusion, these studies indicate that ambient concentrations o f ozone may induce ah-way inflammation, through release of proinflamma tory mediators from airway epithelial cells, This effect may be inhibi ted both by the anti-inflammatory drug, nedocromil sodium, and the nat urally occurring antioxidant glutathione.