ToxSci Advance Access originally published online on March 17, 2009
Toxicological Sciences 2009 109(1):113-123; doi:10.1093/toxsci/kfp057
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Single-Walled and Multi-Walled Carbon Nanotubes Promote Allergic Immune Responses in Mice
* Division of Environmental Medicine, Norwegian Institute of Public Health, NO-0403 Oslo, Norway
National Research Centre for the Working Environment, DK-2100, Copenhagen, Denmark
SINTEF Materials and Chemistry, NO-7465, Trondheim, Norway
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, NO-7489, Trondheim, Norway
1 To whom correspondence should be addressed at Division of Environmental Medicine, Norwegian Institute of Public Health, PO Box 4404 Nydalen, Lovisenbergata 8, NO-0403 Oslo, Norway. Fax: +47 2107 6686. E-mail: unni.cecilie.nygaard{at}fhi.no.
Received December 22, 2008; accepted March 4, 2009
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Abstract |
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The adjuvant effect of particles on allergic immune responses has been shown to increase with decreasing particle size and increasing particle surface area. Like ultrafine particles, carbon nanotubes (CNTs) have nano-sized dimensions and a large relative surface area and might thus increase allergic responses. Therefore, we examined whether single-walled (sw) and multi-walled (mw) CNTs have the capacity to promote allergic responses in mice, first in an sc injection model and thereafter in an intranasal model. Balb/cA mice were exposed to three doses of swCNT, mwCNT, as well as ultrafine carbon black particles (ufCBPs, Printex90) during sensitization with the allergen ovalbumin (OVA). Five days after an OVA booster, OVA-specific IgE, IgG1, and IgG2a antibodies in serum and the numbers of inflammatory cells and cytokine levels in bronchoalveolar lavage fluid (BALF) were determined. Furthermore, ex vivo OVA-induced cytokine release from mediastinal lymph node (MLN) cells was measured. In separate experiments, differential cell counts were determined in BALF 24 h after a single intranasal exposure to the particles in the absence of allergen. We demonstrate that both swCNT and mwCNT together with OVA strongly increased serum levels of OVA-specific IgE, the number of eosinophils in BALF, and the secretion of Th2-associated cytokines in the MLN. On the other hand, only mwCNT and ufCBP with OVA increased IgG2a levels, neutrophil cell numbers, and tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels in BALF, as well as the acute influx of neutrophils after exposure to the particles alone. This study demonstrates that CNTs promote allergic responses in mice.
Key Words: carbon nanotubes; adjuvant effect; airway inflammation; allergy; mice; IgE.
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