The Significance and Insignificance of Carbon Nanotube-Induced Inflammation

Abstract

In the present review article immune responses induced by carbon nanotubes (CNTs) are addressed. As inhalation is considered to be the primary entry route, and concern has been raised by similar high aspect ratio materials, the main focus lies on immune responses upon pulmonary exposure. Inflammation-related findings from both in vivo studies and in vitro models are reviewed, and the major responsible characteristics, which may drive CNT-induced inflammation in the lung, are discussed. In a second part, responses upon intentional administration of CNTs via subcutaneous and intravenous application are addressed, including their potential benefits and drawbacks for immunotherapy. Finally, the gastrointestinal tract as an alternative exposure route is briefly discussed. While there are many studies identifying numerous other factors involved in CNT-driven toxicity, e.g., cytotoxicity, oxidative stress, and genotoxicity, the focus of this review was kept solely on CNT-induced inflammation. Overall the literature has shown that CNTs are able to induce inflammation, which in some cases was a particularly robust response coinciding with the development of pro-fibrotic conditions. In the majority of cases the greatest inflammatory responses were associated with CNTs of considerable length and a high aspect ratio, accompanied by other factors like dispersion and sample purity.

Gadolinium‐containing carbon nanomaterials for magnetic resonance imaging: Trends and challenges

“…However, due to the well‐known toxicity of carbon nanomaterials and the toxicity of free gadolinium ions, more studies are needed to clarify the clinical application. For instance, previous works reported carbon nanotubes and fullerenes may promote adverse effects, including inflammation, oxidative stress, DNA damage and mutation, malignant transformation, the formation of granulomas and interstitial fibrosis . Also, owing the toxicity of free gadolinium ions, it is essential to carry out bioavailability studies by their potential dissociation from the carbon nanostructure.…”

“…A number of reports have found pristine CNTs remain in lungs for months or even years after pulmonary deposition, even more, the accumulation is associated with chronic inflammation and tissue damage . Particularly, the accumulation of MWCNTs in lungs is associated with fibrotic‐like lesions via non‐resolved chronic inflammation and the chronic exposure to SWCNTs may cause malignant transformation of human lung epithelial cells and induced tumorigenesis in mice . The hepatic accumulation of carbon nanotubes is associated with the induction of a local immune response and liver damage .…”

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

“…In the absence of regulatory exposure limits specific to CNTs or CNFs, these materials are by default grouped in the class of poorly-soluble respirable particles by regulatory agencies; moreover, CNTs and CNFs are high-aspect ratio nanomaterials similar to asbestos fibers (Section “Evidence on possible steps in pathway(s) to lung cancer”), and concern about potential carcinogenicity relates to the fibrous structure as well as biopersistence of CNTs and CNFs. Acute and persistent release of proinflammatory mediators from lung target cells have been used as a biomarker for inflammation induced by exposure to CNTs, as well as asbestos fibers (IARC 2012; Boyles et al 2014). Studies on pulmonary inflammatory effects of CNTs in experimental animals are summarized in Table 3.…”

Mapping differential cellular protein response of mouse alveolar epithelial cells to multi-walled carbon nanotubes as a function of atomic layer deposition coating

“…Activation of the IL-1 signaling pathway occurs as a stress response in order to produce various pro-inflammatory mediators [41]. Several studies have shown that MWCNT exposure causes acute inflammation via inflammasome activation and release of IL-1β that binds to specific receptors on a variety of lung cells to mediate acute inflammation [42–44, 26]. While the IL-1 proteins were not detected in this study due to potential limitation in dynamic range, downstream proteins showed enrichment for IL-1 signaling activation.…”