Pulmonary and intraperitoneal inflammation induced by cellulose fibres.
The inflammatory effects of respirable cellulose fibres were studied in two short-term animal models: intraperitoneal injection in mice, and inhalation in rats. The mouse peritoneal cavity is particularly sensitive to fibrous compared to non-fibrous particles. Both cellulose fibres and the positive control fibre, crocidolite asbestos, were administered in doses ranging from 10(4) to 10(8) fibres and caused marked, dose-dependent recruitment of inflammatory cells to the mouse peritoneal cavity, which was highest 1 day following injection. Crocidolite was much more active than cellulose, despite the mass dose of cellulose being 66 times greater for an equivalent number of fibres. Crocidolite at the higher doses caused inflammation to persist through 7 days. For the inhalation study, rats were exposed daily, 5 days per week, to aerosols of cellulose dust for ca. 3 weeks at a concentration of 1000 fibres ml(-1). Inhalation exposure induced an early inflammatory response in rat lungs, as determined by bronchoalveolar lavage, which peaked at 1 day following the start of inhalation and thereafter declined, despite a further 13 days of exposure over a period of 18 calendar days. In vitro production of the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) by lavaged alveolar macrophages was markedly depressed by the end of the exposure period in cellulose-exposed animals, compared to sham-exposed controls, and this effect was still present in rats that had been allowed to recover for 28 days beyond the end of exposure. We conclude that the cellulose material studied is less inflammogenic than crocidolite and that the extent of the inflammatory response within the lung appears to reduce with continued exposure over a 14-day period.
Cullen
R T
RT
Institute of Occupational Medicine, 8 Roxburgh Place, Edinburgh EH8 9SU, UK. Richard.Cullen@IOMHQ.org.uk
Searl
A
A
Miller
B G
BG
Davis
J M
JM
Jones
A D
AD
D000280:Administration, Inhalation; D000818:Animals; D017638:Asbestos, Crocidolite / Q000032:analysis / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002482:Cellulose / Q000032:analysis / Q000633:toxicity*; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000473:pathology*; D010538:Peritonitis / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D017638:Asbestos, Crocidolite; D002482:Cellulose