A Single Aspiration of Rod-like Carbon Nanotubes Induces Asbestos-like Pulmonary Inflammation Mediated in Part by the IL-1 Receptor

Our plain-English summary of A Single Aspiration of Rod-like Carbon Nanotubes Induces Asbestos-like Pulmonary Inflammation Mediated in Part by the IL-1 Receptor, by E.M. Rydman, M. Ilves, E. Vanhala, et al (Toxicological Sciences, 2015).

The study

• Authors: E.M. Rydman, M. Ilves, E. Vanhala, M. Vippola, M. Lehto, P.A. Kinaret, L. Pylkkänen, M. Happo, M.R. Hirvonen, D. Greco, K. Savolainen, H. Wolff, H. Alenius
• Journal: Toxicological Sciences
• Published: 2015;147(1):140-55
• Cited by: 48 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Carbon nanotubes (CNT) have been eagerly studied because of their multiple applications in product development and potential risks on health. We investigated the difference of two different CNT and asbestos in inducing proinflammatory reactions in C57BL/6 mice after single pharyngeal aspiration exposure. We used long tangled and long rod-like CNT, as well as crocidolite asbestos at a dose of 10 or 40 µg/mouse. The mice were sacrificed 4 and 16 h or 7, 14, and 28 days after the exposure. To find out the importance of a major inflammatory marker IL-1β in CNT-induced pulmonary inflammation, we used etanercept and anakinra as antagonists as well as Interleukin 1 (IL-1) receptor (IL-1R-/-) mice. The results showed that rod-like CNT, and asbestos in lesser extent, induced strong pulmonary neutrophilia accompanied by the proinflammatory cytokines and chemokines 16 h after the exposure. Seven days after the exposure, neutrophilia had essentially disappeared but strong pulmonary eosinophilia peaked in rod-like CNT and asbestos-exposed groups. After 28 days, pulmonary granulomas, goblet cell hyperplasia, and Charcot-Leyden-like crystals containing acidophilic macrophages were observed especially in rod-like CNT-exposed mice. IL-1R-/- mice and antagonists-treated mice exhibited a significant decrease in neutrophilia and messenger ribonucleic acid (mRNA) levels of proinflammatory cytokines at 16 h. However, rod-like CNT-induced Th2-type inflammation evidenced by the expression of IL-13 and mucus production was unaffected in IL-1R-/- mice at 28 days. This study provides knowledge about the pulmonary effects induced by a single exposure to the CNT and contributes to hazard assessment of carbon nanomaterials on airway exposure.

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In plain English

This was an experiment in mice, not a study of people. The authors gave female C57BL/6 mice one dose, breathed in from the throat, of long rod-like or long tangled multi-walled carbon nanotubes, or crocidolite asbestos. Doses were 10 or 40 µg per mouse, and lungs were examined from 4 hours to 28 days later. Rod-like nanotubes caused the fastest and strongest early inflammation. Neutrophils, a type of white blood cell, reached almost 40% of lung-wash cells at 16 hours. At day 7, eosinophils rose with rod-like nanotubes and asbestos. At 28 days, mild neutrophilia persisted only with rod-like nanotubes. Granulomas formed with both nanotube types, more with rod-like ones, and none with asbestos. Anakinra (an IL-1 receptor blocker) and etanercept (a TNF blocker), alone or together, reduced neutrophils 4 hours after rod-like nanotubes. Mice lacking the IL-1 receptor also had fewer early neutrophils. In mice lacking the IL-1 receptor, IL-13 and mucus production at 28 days did not differ from normal mice. The authors concluded that rod-like nanotubes were considerably more potent than asbestos at causing lung inflammation, but that their effects were qualitatively quite similar to those of asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: single pharyngeal aspiration exposure in mice, with lungs examined at 4 and 16 hours and 7, 14 and 28 days. Additional experiments used anakinra (IL-1 receptor antagonist), etanercept (TNF inhibitor) and IL-1 receptor knockout mice.
• Who was studied: Female C57BL/6 mice aged 7-8 weeks, plus IL-1 receptor knockout mice on a C57BL/6 background. The figure legends give n=8. Study dates are not stated.
• Exposure: Long tangled multi-walled carbon nanotubes (Cheap Tubes Inc.), long rod-like multi-walled carbon nanotubes (XNRI MWNT-7, Mitsui) and crocidolite asbestos. Doses were 10 µg per mouse for the 4 and 16 hour time points, and 10 or 40 µg per mouse for the 7, 14 and 28 day time points.
• Main results:
  • In mice given rod-like nanotubes, neutrophils reached close to 20% of lung lavage cells at 4 hours and almost 40% at 16 hours. This was the fastest and highest reaction of the three materials, and asbestos did not produce it.
  • At 28 days, neutrophilia persisted in mice given rod-like nanotubes, at levels tenfold lower than in the acute phase. Mice given tangled nanotubes or asbestos no longer showed neutrophilia.
  • At 28 days, granulomas were seen in both nanotube groups, with a clearly larger granuloma area in mice given rod-like nanotubes. Asbestos-exposed mice showed no granuloma formation.
  • At day 7, eosinophils infiltrated lung tissue most with rod-like nanotubes. They were also found with asbestos, and few were found with tangled nanotubes.
  • Charcot-Leyden-like crystals were not seen at day 7 in any group. They were present at day 14 in mice given rod-like nanotubes or asbestos, but not in mice given tangled nanotubes.
  • At 28 days, mice given rod-like nanotubes showed a dramatic increase in IL-13 mRNA at both doses. Tangled nanotubes and asbestos showed an insignificant induction.
  • At 4 hours after 10 µg of rod-like nanotubes, anakinra (an IL-1 receptor antagonist) and etanercept (a TNF inhibitor), given separately or together, significantly decreased neutrophils and IL-1β and TNF mRNA compared with the exposed group.
  • Early after rod-like nanotube exposure, IL-1 receptor knockout mice had significantly fewer neutrophils in lung lavage than normal mice. They also had lower mRNA levels of the neutrophil-attracting chemokines CXCL5, CXCL1 and CXCL2.
  • At 28 days after rod-like nanotubes, mice lacking the IL-1 receptor showed no change in TGF-β, IL-13 or mucus production compared with normal mice.
• The authors' conclusion: The authors concluded that rod-like nanotubes were considerably more potent at inducing lung inflammation than asbestos or tangled nanotubes, but that their effects were qualitatively quite similar to those caused by asbestos.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Inflammation, Crocidolite, Cytokine, Granuloma, Macrophage.

Related studies

• Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs — P. Kinaret, M. Ilves, et al. (2017)
• Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation — E.M. Rydman, M. Ilves, et al. (2014)
• Fibrous nanocellulose, crystalline nanocellulose, carbon nanotubes, and crocidolite asbestos elicit disparate immune responses upon pharyngeal aspiration in mice — E.J. Park, T.O. Khaliullin, et al. (2018)
• Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice — J.G. Teeguarden, B.J. Webb-Robertson, et al. (2011)
• Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos — A.R. Murray, E.R. Kisin, et al. (2012)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)

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