Cp. Pasquale et al., Systemic and local dexamethasone treatments prevent allergic eosinophilia in rats via distinct mechanisms, EUR J PHARM, 368(1), 1999, pp. 67-74
We have studied the effect of local and systemic treatment with dexamethaso
ne for prevention of the pleural eosinophilia triggered by allergen in acti
vely sensitised Wistar rats. Parallel changes in blood and marrow eosinophi
l numbers were assessed for comparison. The intrapleural (i.pl.) injection
of ovalbumin into ovalbumin-sensitised animals led to a long-lasting pleura
l fluid eosinophilia which peaked from 24 to 72 h post-challenge. At these
time points, there was a significant 2- to 3-fold increase in the blood eos
inophil numbers, whereas the bone marrow number of mature eosinophils remai
ned unaltered. Systemic treatment with dexamethasone (0.05-0.5 mg/kg, i.p.)
abolished the pleural and blood eosinophilia observed 24 and 48 h post-cha
llenge, also causing a significant reduction in marrow eosinophil numbers.
Despite being unable to alter blood and bone marrow eosinophil numbers, the
local i.pl, administration of dexamethasone (2.5-10 mu g/cavity) inhibited
dose dependently the allergen-induced pleural eosinophil influx at 24 h bu
t not at 48 h post-challenge. This treatment also shortened the time course
of eosinophil accumulation in the pleural space from the 48 h time point o
n. We conclude that the effect of systemic but not of local treatment with
dexamethasone on allergen-induced eosinophil recruitment is well correlated
with the inhibition of eosinophil production in bone marrow. In contrast,
low amounts of dexamethasone injected into the pleural space seem to affect
locally eosinophil recruitment and survival. (C) 1999 Elsevier Science B.V
. All rights reserved.