Mia Johansson1, Åsa Gustafsson2,3, Gunnar Johanson1, Mattias Öberg1,3. 1. a Institute of Environmental Medicine, Karolinska Institutet , Stockholm , Sweden. 2. b Swedish Defense Research Agency (FOI) , Umeå , Sweden. 3. c Swedish Toxicology Sciences Research Center (Swetox) , Södertälje , Sweden.
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.
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.
Authors: Niels Hadrup; Marie Frederiksen; Eva B Wedebye; Nikolai G Nikolov; Tanja K Carøe; Jorid B Sørli; Karen B Frydendall; Biase Liguori; Camilla S Sejbaek; Peder Wolkoff; Esben M Flachs; Vivi Schlünssen; Harald W Meyer; Per A Clausen; Karin S Hougaard Journal: J Appl Toxicol Date: 2021-07-11 Impact factor: 3.628