Title: Inhalation exposure to multi-walled carbon nanotubes alters the pulmonary allergic response of mice to house dust mite allergen.

Authors: Ihrie, Mark D; Taylor-Just, Alexia J; Walker, Nigel J; Stout, Matthew D; Gupta, Amit; Richey, Jamie S; Hayden, Barry K; Baker, Gregory L; Sparrow, Barney R; Duke, Katherine S; Bonner, James C

Published In Inhal Toxicol, (2019 04)

Abstract: Background: Increasing evidence from rodent studies indicates that inhaled multi-walled carbon nanotubes (MWCNTs) have harmful effects on the lungs. In this study, we examined the effects of inhalation exposure to MWCNTs on allergen-induced airway inflammation and fibrosis. We hypothesized that inhalation pre-exposure to MWCNTs would render mice susceptible to developing allergic lung disease induced by house dust mite (HDM) allergen. Methods: Male B6C3F1/N mice were exposed by whole-body inhalation for 6 h a day, 5 d a week, for 30 d to air control or 0.06, 0.2, and 0.6 mg/m3 of MWCNTs. The exposure atmospheres were agglomerates (1.4-1.8 µm) composed of MWCNTs (average diameter 16 nm; average length 2.4 µm; 0.52% Ni). Mice then received 25 µg of HDM extract by intranasal instillation 6 times over 3 weeks. Necropsy was performed at 3 and 30 d after the final HDM dose to collect serum, bronchoalveolar lavage fluid (BALF), and lung tissue for histopathology. Results: MWCNT exposure at the highest dose inhibited HDM-induced serum IgE levels, IL-13 protein levels in BALF, and airway mucus production. However, perivascular and peribronchiolar inflammatory lesions were observed in the lungs of mice at 3 d with MWCNT and HDM, but not MWCNT or HDM alone. Moreover, combined HDM and MWCNT exposure increased airway fibrosis in the lungs of mice. Conclusions: Inhalation pre-exposure to MWCNTs inhibited HDM-induced TH2 immune responses, yet this combined exposure resulted in vascular inflammation and airway fibrosis, indicating that MWCNT pre-exposure alters the immune response to allergens.

PubMed ID: 31345048

MeSH Terms: Animals; Antigens, Dermatophagoides/immunology*; Bronchoalveolar Lavage Fluid; Dose-Response Relationship, Immunologic; Fibrosis; Hypersensitivity/physiopathology*; Immunoglobulin E/blood; Inhalation Exposure/adverse effects*; Interleukin-13/analysis; Lung/physiology*; Male; Mice; Nanotubes, Carbon/toxicity*; Th2 Cells/immunology