Contribution of IL-1[beta] and TNF-[alpha] to the initiation of the peripheral lung response to atmospheric particulates (P[M.sub.10])

Alveolar macrophages (AM) play a key role in clearing atmospheric particulates from the lung surface and stimulating epithelial cells to produce proinflammatory mediators. The present study examines the role of 'acute response' cytokines TNF-[alpha] and IL-1[beta] released by AM exposed to ambient particulate matter with a diameter of 0.05), and the combination of the two antibodies most effective. When HBEC were treated similarly, anti-TNF-[alpha] antibodies had the greatest effect. In A549 cells P[M.sub.10]-exposed AM supernatants increased NF-[kappa]B, activator protein (AP)-1 and specificity protein 1 binding, while anti-TNF-[alpha] and anti-IL-1[beta] antibodies reduced NF-[kappa]B and AP-1 binding. We conclude that AM-derived TNF-[alpha] and IL-1[beta] provide a major stimulus for the production of proinflammatory mediators by lung epithelial cells and that their relative importance may depend on the type of epithelial cell target. ribonuclease protection assay; transcription factors; enzyme-linked immunosorbent assay; proinflammatory mediators; particulate matter with diameter < 10 [micro]m