Comparison of airway response in naïve and ovalbumin-sensitized mice during short-term inhalation exposure to chlorine

Abstract

Objective: It has been suggested that asthmatics are more susceptible than healthy individuals to airborne irritating chemicals in general. However, there is limited human data available to support this hypothesis due to ethical and practical difficulties. We explored a murine model of ovalbumin (OVA)-induced airway inflammation to study susceptibility during acute exposure to chemicals with chlorine as a model substance.

Methods: Naïve and OVA sensitized female BALB/c mice were exposed to chlorine at four different concentrations (0, 5, 30 and 80 ppm) for 15 minutes with online recording of the respiratory function by plethysmography. The specific effects on respiratory mechanics, inflammatory cells and inflammatory mediators (cytokines and chemokines) of the airways were measured 24 hours after the chlorine exposure as well as histopathological examination of the lungs.

Results: Similar concentration-dependent reductions in respiratory frequency were seen in the two groups, with a 50% reduction (RD₅₀) slightly above 5 ppm. Decreased body weight 24 hours after exposure to 80 ppm was also observed in both groups. Naïve, but not OVA-sensitized, mice showed increased bronchial reactivity and higher number of neutrophils in bronchoalveolar lavage fluid at 80 ppm.

Conclusions: The results do not support an increased susceptibility to chlorine among OVA-sensitized mice. This animal model, which represents a phenotype of eosinophilic airway inflammation, seems unsuitable to study susceptibility to inhalation of irritants in relation to asthma.

Keywords:

• airway inflammation
• asthma
• chlorine
• mice
• susceptibility

Acknowledgements

We are grateful to Linda Elfsmark, Sivert Graff, Bo Koch, Maritha Marcusson-Ståhl, Elisabeth Wigenstam and Lina Ågren for technical assistance. This project was performed within the National Centre for Disaster Toxicology (KcC), funded by the Swedish National Board of Health and Welfare (44668/2012) and the Swedish Civil Contingencies Agency (15523/2011). The parts performed at Swetox were supported by Stockholm County Council, Knut & Alice Wallenberg Foundation, and the Swedish Research Council FORMAS.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This project was performed within the National Centre for Disaster Toxicology (KcC), funded by the Swedish National Board of Health and Welfare (44668/2012) and the Swedish Civil Contingencies Agency (15523/2011). The parts performed at Swetox were supported by Stockholm County Council, Knut & Alice Wallenberg Foundation, and the Swedish Research Council FORMAS.