Am. J. Respir. Cell Mol. Biol., Volume 20, Number 5, May, 1999 1013-1019

Influence of Ozone and Nitrogen Dioxide on Histamine and Interleukin Formation in a Human Nasal Mucosa Culture System

Katrin Schierhorn, Minzhong Zhang, Christoph Matthias, and Gert Kunkel

Department of Clinical Immunology and Asthma-OPD, and Department of Otorhinolaryngology, Virchow-Klinikum, Humboldt-University, Berlin, Germany

There is evidence that asthma and other allergic diseases are increasing and air pollution has been considered an important contributing factor to this observation. Using a specially designed organ culture system, we examined the influence of ozone (0.06 to 0.2 ppm) and nitrogen dioxide (NO₂, 200 and 800 µg/m³) on nasal mucosa exposed for 24 h. Tissue was obtained from 105 patients undergoing surgical therapy (septoplasty and reduction of the inferior turbinates) for chronic nasal obstruction. The histamine content in the culture medium of ozone- and NO₂-exposed samples was significantly elevated compared with the control cultures. This elevation was correlated with the number of degranulated mast cells in the tissue determined by histomorphometry (P < 0.001). Moreover, the cytokines interleukin (IL)-1 (P < 0.05), IL-6 (P < 0.01), IL-8 (P < 0.001), and tumor necrosis factor- (TNF-, P < 0.001) were significantly increased (ozone 0.1 ppm). Furthermore, we found significant increases in the release of IL-4, IL-6, IL-8, and TNF- of ozone-exposed (0.1 ppm) samples of atopic versus nonatopic patients and to a lesser extent for histamine following exposure to 0.15 ppm ozone. These results indicate that low ozone concentrations and NO₂ lead to an inflammation of human nasal mucosa in vitro and that priming factors such as atopy or preexisting inflammation do increase the sensitivity to ozone and NO₂. This organ culture system proved to be a good experimental design for studying pathophysiologic alterations of human nasal mucosa under different experimental conditions (e.g., air pollutants).

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