Airway inflammation after inhalation of nano-sized zinc oxide particles in human volunteers

Background: Workers in the zinc production and processing of galvanized sheet steel are exposed to a complex mixture of particles and gases, including zinc oxide (ZnO) that can affect human health. We aimed to study the effects of short-term controlled exposure to nano-sized ZnO on airway inflammatory markers in healthy volunteers. Methods: Sixteen subjects (8 females, 8 men; age 19-42, non-smokers) were exposed to filtered air and ZnO nanoparticles (0.5, 1.0 and 2.0 mg/m(3)) for 4 h, including 2 h of cycling with a low workload. Induced sputum samples were collected during a medical baseline and a final examination and also about 24 h after each exposure. A number of inflammatory cellular and soluble markers were analyzed. Results: Frequency and intensity of symptoms of airway irritation (throat irritation and cough) were increased in some subjects 24 h after ZnO exposures when compared to filtered air. The group comparison between filtered air and ZnO exposures showed statistically significant increases of neutrophils and interleukin-8 (IL-8), interleukin-6 (IL-6), matrix metalloproteinase (MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1) in sputum starting at the lowest ZnO concentration of 0.5 mg/m(3). However, a concentration-response relationship was absent. Effects were reversible. Strong correlations were found between neutrophil numbers and concentrations of total protein, IL-8, MMP-9, and TIMP-1. Conclusions: Controlled exposures of healthy subjects to ZnO nanoparticles induce reversible airway inflammation which was observed at a concentration of 0.5 mg/m(3) and higher. The lack of a concentration-response relationship warrants further studies.