Pulmonary inflammation and injury induced by exposure to environmental air pollutants

Exposure to environmental air pollutants produces health effects and exacerbates preexisting respiratory diseases. Ozone is a highly toxic oxidant found in urban environments. Environmental tobacco smoke (ETS) contaminates indoor air in homes and workplaces. In these experiments, a model system of pulmonary inflammation and injury was established by exposing mice to aged and diluted sidestream cigarette smoke (ADSS) as a surrogate of ETS (six hours/day for three days), ozone (0.5 ppm for twenty four hours), or ADSS followed by ozone (ADSS/ozone) to examine the pulmonary effects of ADSS, ADSS effects on ozone-induced lung injury, the role of interleukin (IL)-6 in pulmonary inflammation and injury, and pulmonary production of neurotrophins following exposure to ADSS and/or ozone as well as the regulatory effect of IL-6. Bronchoalveolar lavage was performed to evaluate inflammatory response and bromodeoxyuridine (BrdU) labeling was used to identify cell proliferation as an indicator of lung injury. Cytokine release by alveolar macrophages and pulmonary production of neurotrophin were also examined. Exposure only to ADSS did not cause lung injury. Exposure to ozone induced lung inflammation and injury. Prior exposure to ADSS at a concentration of 30 mg total suspended particullate/m3 significantly augmented ozone-induced injury in the centriacinar regions. In terminal bronchiolar epithelium and the proximal alveolar regions, prior exposure to ADSS augmented ozone injury in a dose response manner. IL-6 deficiency was associated with attenuated inflammation and injury in the lungs following exposure to ozone or ADSS/ozone, while, ADSS enhancement of ozone-induced lung injury was absent in IL-6 null mice. Exposure to ozone induced brain-derived neurotrophic factor production in the lung, which was directly associated with the severity of injury, while exposure to ADSS caused pulmonary production of nerve growth factor, which was mediated by IL-6. Thus, these studies establish a new measure to determine health effect of exposure to ETS, generate new evidence of IL-6 effect on pulmonary inflammation and injury, provide a novel view on the role of IL-6 and neurotrophins as communicators between pulmonary innervation and lung injury.