Pro-inflammatory versus immunomodulatory effects of silver nanoparticles in the lung: The critical role of dose, size and surface modification

Francesca Alessandrini, Antje Vennemann, Silvia Gschwendtner, Avidan U. Neumann, Michael Rothballer, Tanja Seher, Maria Wimmer, Susanne Kublik, Claudia Traidl-Hoffmann, Michael Schloter, Martin Wiemann, Carsten B. Schmidt-Weber

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


The growing use of silver nanoparticles (Ag-NPs) in consumer products raises concerns about their toxicological potential. The purpose of the study was to investigate the size- and coating-dependent pulmonary toxicity of Ag-NPs in vitro and in vivo, using an ovalbumin (OVA)-mouse allergy model. Supernatants from (5.6–45 μg/mL) Ag50-PVP, Ag200-PVP or Ag50-citrate-treated NR8383 alveolar macrophages were tested for lactate dehydrogenase and glucuronidase activity, tumor necrosis factor (TNF)-α release and reactive oxygen species (ROS) production. For the in vivo study, NPs were intratracheally instilled in non-sensitized (NS) and OVA-sensitized (S) mice (1–50 μg/mouse) prior to OVA-challenge and bronchoalveolar lavage fluid (BALF) inflammatory infiltrate was evaluated five days after challenge. In vitro results showed a dose-dependent cytotoxicity of Ag-NPs, which was highest for Ag50-polyvinilpyrrolidone (PVP), followed by Ag50-citrate, and lowest for Ag200-PVP. In vivo 10–50 μg Ag50-PVP triggered a dose-dependent pulmonary inflammatory milieu in NS and S mice, which was significantly higher in S mice and was dampened upon instillation of Ag200-PVP. Surprisingly, instillation of 1 μg Ag50-PVP significantly reduced OVA-induced inflammatory infiltrate in S mice and had no adverse effect in NS mice. Ag50-citrate showed similar beneficial effects at low concentrations and attenuated pro-inflammatory effects at high concentrations. The lung microbiome was altered by NPs instillation dependent on coating and/or mouse batch, showing the most pronounced effects upon instillation of 50 μg Ag50-citrate, which caused an increased abundance of operational taxonomic units assigned to Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. However, no correlation with the biphasic effect of low and high Ag-NPs dose was found. Altogether, both in vitro and in vivo data on the pulmonary effects of Ag-NPs suggest the critical role of the size, dose and surface functionalization of Ag-NPs, especially in susceptible allergic individuals. From the perspective of occupational health, care should be taken by the production of Ag-NPs-containing consumer products.

Original languageEnglish
Article number300
Issue number10
StatePublished - 29 Sep 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.


Acknowledgments: The authors would like to thank Johanna Grosch, Benjamin Schnautz, Katja Haslauer and Alexandra Seisenberger for excellent technical assistance. We are thankful to all contributors to the NanoGEM consortium for providing and carefully characterizing the nanomaterials, and to Thomas Kuhlbusch for the excellent coordination of the NanoGEM Project. This study was supported by the German Federal Ministry of Education and Research (BMBF) NanoGEM Project, under the accession numbers 03X0105H (given to Martin Wiemann), and 03X0105O (given to Francesca Alessandrini).

FundersFunder number
Bundesministerium für Bildung und Forschung03X0105H, 03X0105O


    • Adjuvant
    • Allergic inflammation
    • Silver nanoparticles
    • Surface modification


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