Inhalation exposure of nano-scaled titanium dioxide (TiO₂) particles alters the inflammatory responses in asthmatic mice

Abstract

Context: Titanium dioxide (TiO₂) nanoparticles (NPs) are regarded as relatively non-toxic in concentrations occurring in occupational environments. Nevertheless, it is conceivable that adverse health effects may develop in sensitive populations such as individuals with respiratory diseases.

Objective: We investigated whether single or repeated exposure to TiO₂ could aggravate inflammatory responses in naïve mice and mice with ovalbumin (OVA)-induced airway inflammation.

Methods: Exposure to aerosolized TiO₂ was performed during OVA sensitization, before, or during the OVA challenge period. The effects on respiratory physiology, inflammatory cells in bronchoalveolar lavage (BAL) and inflammatory mediators in BAL and serum were assessed 24 h after the last OVA challenge or TiO₂ exposure.

Results: A single exposure of TiO₂ had a marked effect on responses in peripheral airways and increasing infiltration of neutrophils in airways of naïve animals. Marked aggravation of airway responses was also observed in animals with allergic disease provided that the single dose TiO₂ was given before allergen challenge. Repeated exposures to TiO₂ during sensitization diminished the OVA-induced airway eosinophilia and airway hyperresponsiveness but concomitant exposure to TiO₂ during the OVA challenge period resulted in neutrophilic airway inflammation and a decline in general health condition as indicated by the loss of body weight.

Conclusion: We conclude that inhalation of TiO₂ may aggravate respiratory diseases and that the adverse health effects are highly dependent on dose and timing of exposure. Our data imply that inhalation of NPs may increase the risk for individuals with allergic airway disease to develop symptoms of severe asthma.

• Asthma
• inflammation
• nanomaterial
• respiratory mechanics
• titanium dioxide

Acknowledgements

The authors would like to thank Ola Nerbrink, Linda Elfsmark, Christine Akfur, Lina Thors, Lina Ågren, Karin Wallgren, and Christian Lejon for technical assistance.