Volatile organic compounds enhance allergic airway inflammation in an experimental mouse model.
BACKGROUND
Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear.


METHODS
To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs.


RESULTS
Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation.


CONCLUSIONS
Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases.
Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, Leipzig, Germany.
Ulrike
U
Bönisch
Alexander
A
Böhme
Tibor
T
Kohajda
Iljana
I
Mögel
Nicole
N
Schütze
Martin
M
von Bergen
Jan C
JC
Simon
Irina
I
Lehmann
Tobias
T
Polte
D000111:Acetylcysteine / Q000627:therapeutic use; D016902:Air Pollution, Indoor / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005430:Floors and Floorcoverings; D006018:Glycols / Q000009:adverse effects*; D018664:Interleukin-12 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced*; D011143:Polyvinyl Chloride / Q000009:adverse effects; D011760:Pyrrolidinones / Q000009:adverse effects*; D018418:Th2 Cells / Q000276:immunology; D055549:Volatile Organic Compounds / Q000009:adverse effects*
D006018:Glycols; D011760:Pyrrolidinones; D055549:Volatile Organic Compounds; D018664:Interleukin-12; C001508:2,2,4-trimethyl-1,3-pentanediol diisobutyrate; D011143:Polyvinyl Chloride; D010047:Ovalbumin; C038678:N-methylpyrrolidone; D000111:Acetylcysteine