ToxSci Advance Access published online on March 17, 2009
Toxicological Sciences, 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, P.O.Box 4404 Nydalen, NO-0403 Oslo, Norway
National Research Centre for the Working Environment, Copenhagen, Denmark
SINTEF Materials and Chemistry, Trondheim, Norway
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
1 To whom the correspondence should be addressed: Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, Delivery address: Lovisenbergata 8, NO-0403 Oslo, Norway. Telephone: +47 2107 6435, Fax +47 2107 6686 E-mail address: unni.cecilie.nygaard{at}fhi.no
Received December 22, 2008; revision received March 4, 2009; 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 (CNT) 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) CNT have the capacity to promote allergic responses in mice, first in a subcutaneous 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 (ufCBP, 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. Further, 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 hours after a single intranasal exposure to the particles in the absence of allergen. We demonstrate that both sw and mw CNT 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 TNF-
and MCP-1 levels in BALF, as well as the acute influx of neutrophils after exposure to the particles alone. This study demonstrates that CNT promote allergic responses in mice.
Key Words: carbon nanotubes; adjuvant effect; airway inflammation; allergy; mice; IgE.