title: Titanium dioxide induced inflammation in the small intestine.
abstract: OBJECTIVE
  To investigate the effects of titanium dioxide (TiO₂) nanoparticles (NPTiO₂) and microparticles (MPTiO₂) on the inflammatory response in the small intestine of mice.
  
  
  METHODS
  Bl 57/6 male mice received distilled water suspensions containing TiO₂ (100 mg/kg body weight) as NPTiO₂ (66 nm), or MPTiO₂ (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4+ and CD8+ T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immunohistochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry.
  
  
  RESULTS
  We found increased levels of T CD4+ cells (cells/mm²) in duodenum: NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum: NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum: NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO₂ showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE): IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99 ± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P < 0.05); and TGF-β: NP 780.70 ± 318.50, MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05).
  
  
  CONCLUSIONS
  Our findings indicate that TiO₂ particles induce a Th1-mediated inflammatory response in the small bowel in mice.
authors.affiliation: Laboratory of Clinical and Experimental Gastroenterology, Department of Gastroenterology, School of Medicine, University of São Paulo, Cerqueira César, 01246-900 São Paulo, Brazil.
authors.forename: Carolina Maciel
authors.initials: CM
authors.lastname: Nogueira
authors.forename: Walter Mendes
authors.initials: WM
authors.lastname: de Azevedo
authors.forename: Maria Lucia Zaidan
authors.initials: ML
authors.lastname: Dagli
authors.forename: Sérgio Hiroshi
authors.initials: SH
authors.lastname: Toma
authors.forename: André Zonetti de Arruda
authors.initials: AZ
authors.lastname: Leite
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Lordello
authors.forename: Iêda
authors.initials: I
authors.lastname: Nishitokukado
authors.forename: Carmen Lúcia
authors.initials: CL
authors.lastname: Ortiz-Agostinho
authors.forename: Maria Irma Seixas
authors.initials: MI
authors.lastname: Duarte
authors.forename: Marcelo Alves
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Aytan Miranda
authors.initials: AM
authors.lastname: Sipahi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis; D004751:Enteritis / Q000139:chemically induced*; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D014025:Titanium / Q000633:toxicity*
chemical_list: D016207:Cytokines; C009495:titanium dioxide; D014025:Titanium