Episodic ozone exposure over two weeks alters pulmonary inflammation and gene expression in Long-Evans rats

Elevated exposure to ozone (O₃) may occur episodically over short windows of time. However, laboratory investigations have consistently shown that repeated ozone exposures produce an adaptation response, reducing the effects of O₃ on ventilatory function. To better understand these responses, we developed a rodent model of episodic O₃ exposure to characterize differing exposure patterns on pulmonary toxicity.

Male, Long-Evans rats were exposed for either two days or two weeks of episodic exposure to 0.4 or 0.8 ppm O₃ (4 h/day). Rats in the two-week group were exposed for a total of five nonconsecutive days, with one- to four-day periods of recovery between each exposure. Whole body plethysmography was performed following each exposure. Markers of lung injury and inflammation in the bronchoalveolar lavage fluid were measured, and lung expression of select genes were assessed using qPCR ∼24 h after the final exposure.

Concentration-dependent effects of O₃ on breathing parameters and lung injury were observed following two days of exposure. However, these responses were less evident in rats exposed episodically over two weeks. Comparable increases in bronchoalveolar lavage fluid inflammatory cells and cytokine concentrations were observed irrespective of exposure duration. Furthermore, reduced expression of genes involved in neuroendocrine signaling was detected only following two weeks of episodic exposure (Adrb2, Nr3c1, Dusp1, Glccl1).

Aspects of the adaptation response were still present in rats episodically exposed to O₃ over two weeks. On the other hand, O₃-mediated alterations in pulmonary immune populations show continued responsiveness in this model, suggesting that adaptation may be endpoint specific.