Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice

Our plain-English summary of Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice, by A. Yamaguchi, T. Fujitani, K. Ohyama, et al (The Journal of Toxicological Sciences, 2012).

The study

• Authors: A. Yamaguchi, T. Fujitani, K. Ohyama, D. Nakae, A. Hirose, T. Nishimura, A. Ogata
• Journal: The Journal of Toxicological Sciences
• Published: 2012;37(1):177-89
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Possible effects of multi-wall carbon nanotubes (MWCNTs) on immune and inflammatory responses were examined in mice. Female ICR mice were given a single intraperitoneal administration (2 mg/kg body weight) of either MWCNTs, carbon black (CB), or crocidolite (blue asbestos) and controls received a vehicle of 2% sodium carboxymethyl cellulose (CMC Na). In the peritoneal cavity of MWCNT-administered mice, the liver had changed to a rounded shape and fibrous adhesions were seen on internal organs. Peritoneal cells overexpressed mRNA for genes of T helper (Th)2 cytokines (interleukin [IL]-4, IL-5, and IL-13), Th17 cytokine (IL-17), pro-inflammatory cytokines/chemokines (IL-1β, IL-33, tumor necrosis factor α, and monocyte chemotactic protein-1), and myeloid differentiation factor 88 for at least 2 weeks after the administration of MWCNTs, while those of Th1 cytokine genes (IL-2 and interferon γ) were overexpressed several weeks later and expression levels remained high up to 20 weeks. In MWCNT-treated mice, the numbers of leukocytes, monocytes, and granulocytes in the peripheral blood and the expression of the leukocyte adhesion molecules, cluster of differentiation (CD)49d and CD54, on granulocytes were increased 1 week after administration and remained high up to week 20. Production of ovalbumin-specific IgM and IgG(1) was enhanced by MWCNTs. These changes were not observed after CB or crocidolite administration. Thus, this study showed that MWCNTs exhibited sustained stimulating effects on immune and inflammatory responses, unlike the other mineral fibers with structural similarities.

In plain English

This was an animal experiment in female ICR mice in Japan. In three separate experiments, mice received one abdominal injection (2 mg/kg body weight) of multi-wall carbon nanotubes (MWCNTs), carbon black, or crocidolite (blue asbestos). Control mice received only the carrier liquid. In MWCNT-treated mice, fibrous adhesions formed on internal organs and the lining of the liver thickened. Abdominal-cavity cells showed raised activity of several immune and inflammation genes over many weeks. IL-5 gene activity, for example, was 63 to 226 times baseline. Blood white cell counts rose from week 1 to week 20, and antibody responses to a test protein were higher. In the first experiment, 2 of 6 MWCNT-treated mice died within 32 weeks. No tumors were seen in any treated mice within the 34-week experimental period. Crocidolite caused a sustained rise in one gene (IL-6) and a minimal, short-lived rise in white cells at week 1. The authors concluded that MWCNTs had sustained stimulating effects on immune and inflammatory responses, unlike carbon black and crocidolite. They said further investigation is needed before applying these animal results to human health.

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: three independent mouse experiments, each using a single intraperitoneal injection, with follow-up of up to 34 weeks
• Who was studied: Specific pathogen-free female Crlj:CD1(ICR) mice, 6-7 weeks old, studied at the Tokyo Metropolitan Institute of Public Health, Japan. Group sizes were 3-6 per group per time point in the first experiment, 4 per group per time point in the second, and 10-19 (IgM) or 15 (IgG1) per group in the third. The article does not give total numbers or study dates.
• Exposure: A single intraperitoneal dose of 2 mg/kg body weight of MWCNTs (MITSUI MWCNT-7), carbon black (22 nm), or UICC-grade crocidolite, each suspended in 2% sodium carboxymethyl cellulose (CMC Na). Controls received CMC Na alone.
• Main results:
  • In MWCNT-treated mice, fibrous adhesions were seen on internal organs and deposits on the surfaces of the liver and diaphragm.
  • In MWCNT-treated mice, the hepatic visceral peritoneum showed fibrous thickening with mesothelial cell hypertrophy.
  • No tumorigenic changes were observed, either by eye or under the microscope, in any treated mouse within the 34-week experimental period.
  • Deaths in the first animal experiment: 2 of 6 MWCNT-treated mice died within 32 weeks.
  • In peritoneal cells of MWCNT-treated mice, IL-5 mRNA was 110, 127, 63, 226 and 69 times higher than the basal control at 2, 4, 10, 20 and 34 weeks.
  • In MWCNT-treated mice, the Th1 cytokine genes IL-2 and IFNγ were not significantly above basal levels, except IL-2 at 34 weeks.
  • In crocidolite-treated mice, IL-6 mRNA was 4, 5, 6 and 8 times higher at 2, 4, 10 and 20 weeks.
  • In MWCNT-treated mice, blood leukocytes, granulocytes and monocytes were increased from 1 to 20 weeks.
  • In crocidolite-treated mice, leukocytes, granulocytes and monocytes showed a statistically significant but minimal, transient increase at week 1.
  • Carbon black and crocidolite did not induce overexpression of leukocyte adhesion molecules on blood cells.
  • Ovalbumin-specific IgM, in arbitrary units (mean, plus or minus the spread in brackets), was 1.33 (0.20) for MWCNTs, 1.07 (0.20) for carbon black, 1.07 (0.15) for crocidolite, and 0.79 (0.12) for CMC Na controls.
  • Ovalbumin-specific IgG1, in arbitrary units (mean, plus or minus the spread in brackets), was 3.68 (0.57) for MWCNTs, 2.49 (0.29) for carbon black, 2.13 (0.32) for crocidolite, and 2.28 (0.35) for controls. Only MWCNTs significantly enhanced antibody production.
• The authors' conclusion: The authors concluded that, under their experimental conditions, MWCNTs had sustained stimulating effects on immune and inflammatory responses, unlike the other materials tested, which they described as mineral fibers with structural similarities.
• Limitations the authors state:
  • Intraperitoneal administration may not be directly relevant to humans.
  • Further investigation is required before the animal data can be applied to human health.
  • The vehicle (CMC Na) may itself have had a small effect.

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Peritoneal Cavity, Cytokine, Necrosis, Mineral Fiber.

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