Effects of ozone on macrophage adhesion in vitro and epithelial and inflammatory responses in vivo: The role of cytokines

Inhalation exposure to ozone (O-3) is known to induce epithelial and inflammatory changes in the lungs, characterized by neutrophilia and changes in epithelial permeability. Several cell types and their soluble mediators, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), are involved in the evolution of these responses. In this study, we have compared the effects of the combination of anti-IL-1 alpha and anti-TNF-alpha on in vitro and in vivo responses to inhaled O-3. Male, Sprague-Dawley rats were exposed, nose-only, to 0.8 ppm O-3 for 3 h and the in vitro and in vivo parameters were measured 8-12 h following exposure. The in vitro studies revealed that the adherence of inflammatory cells, primarily macrophages, harvested from the lungs of O-3-exposed rats to cultured lung epithelial cells (ARL-14) was significantly greater than the adherence of macrophages from air-exposed controls. Furthermore, this adherence was significantly reduced in antibody-treated cells as compared to cells treated with preimmune rabbit serum. In vivo, elevations were found in the percentage of neutrophils in bronchoalveolar lavage fluid (BALF), transport of Tc-99m-diethylenetriaminepentaacetate (DTPA) across the tracheal epithelium, and concentrations of total protein and albumin in BALF following O-3 exposure. However, these effects were not significantly altered by treatment with the anti-IL-1 alpha/anti-TNF-alpha combination. Therefore it was concluded that O-3 affects the early stages of the inflammatory response, particularly with respect to macrophage activation and adherence to epithelial cells, and that this early response may be mediated by IL-1 alpha and/or TNF-alpha. The results also suggest that the in vivo effects of O-3 are controlled by complex mechanisms involving factors other than IL-1 alpha and TNF-alpha, even though these cytokines are capable of modifying macrophage function as revealed by the in vitro adherence studies.