title: Pulmonary toxicity of polyvinyl chloride particles after repeated intratracheal instillations in rats. Elevated CD4/CD8 lymphocyte ratio in bronchoalveolar lavage.
abstract: Occupational exposure to polyvinyl chloride (PVC) particles has been associated with interstitial lung disease. Our previous study showed that a single intratracheal instillation of emulsion PVC particles, with or without residual additives, induces acute but transient alveolitis in a dose-dependent manner in rats. The aim of the present study was to investigate the pulmonary response after the administration of the same PVC particles (PVC-E3 and PVC-W3) given in the same cumulative doses (10 and 50 mg/kg BW), but fractionated as seven intratracheal instillations (7 x 1.4 and 7 x 7.1 mg/kg BW) in the course of 3 weeks (day 0 to day 21). Pulmonary response was characterized by analysis of lung weight, bronchoalveolar lavage (BAL) fluid for lactate dehydrogenase (LDH), total protein, and cell cytology, and a microscopic evaluation of lung tissue. BAL T lymphocyte phenotypes (CD3 + CD4 +, CD3 + CD8+) were analyzed by flow cytometry. On day 28, lung weights, BAL-LDH, cell numbers in BAL, and CD4/CD8 ratios in BAL T lymphocytes were higher in rats that had received the high dose of PVC-E3 or PVC-W3 than in rats that had received the low dose of PVC particles and control rats. On day 90, the pulmonary response had partially regressed towards control values, but there were still microscopically evident lesions in the lungs and greater CD4/CD8 ratio in the high dose groups. There were significant positive correlations between the CD4/CD8 ratio and a histopathology score of the lung (r = 0.36, P = 0.038 on day 28, and r = 0.46, P = 0.006 on day 90). In conclusion, repeated intratracheal instillations of PVC particles yielded similar results as single instillations. The examined PVC particles have the potential of inducing a limited and transient acute inflammatory reaction in the lung, and possibly a more persistent alteration of pulmonary T lymphocyte subsets towards a high CD4/CD8 ratio.
authors.affiliation: Laboratory of Pneumology, Unit of Lung Toxicology, K.U. Leuven, Belgium.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Hadewijch M
authors.initials: HM
authors.lastname: Vanhooren
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.forename: Lisong
authors.initials: L
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.forename: Benoit
authors.initials: B
authors.lastname: Nemery
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D016516:CD4-CD8 Ratio / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D004334:Drug Administration Schedule; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011143:Polyvinyl Chloride / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011143:Polyvinyl Chloride; D007770:L-Lactate Dehydrogenase