The inflammatory effects of respirable cellulose fibres were studied in two
short-term animal models: intraperitoneal injection in mice, and inhalatio
n in rats,
The mouse peritoneal cavity is particularly sensitive to fibrous compared t
o non-fibrous particles. Both cellulose fibres and the positive control fib
re, 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 inj
ection. Crocidolite was much more active than cellulose, despite the mass d
ose of cellulose being 66 times greater for an equivalent number of fibres,
Crocidolite at the higher doses caused inflammation to persist through 7 d
ays.
For the inhalation study, rats were exposed daily, 5 days per week, to aero
sols of cellulose dust for ca, 3 weeks at a concentration of 1000 fibres ml
(-1). Inhalation exposure induced an early inflammatory response in rat lun
gs, as determined by bronchoalveolar lavage, which peaked at 1 day followin
g the start of inhalation and thereafter declined, despite a further 13 day
s of exposure over a period of 18 calendar days. In vitro production of the
pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) by lava
ged 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 lun
g appears to reduce with continued exposure over a 14-day period. Copyright
(C) 2000 John Wiley & Sons, Ltd.