A. Tailor et al., Dexamethasone inhibition of leucocyte adhesion to rat mesenteric postcapillary venules: role of intercellular adhesion molecule 1 and KC, GUT, 45(5), 1999, pp. 705-712
Background-A previous study showed that the glucocorticoid dexamethasone, a
t doses of 100 mu g/kg and above, inhibited leucocyte adhesion to rat mesen
teric postcapillary venules activated with interleukin Ip (IL-1 beta), as a
ssessed by videomicroscopy.
Aims-To identify whether the adhesion molecule, intercellular adhesion mole
cule 1 (ICAM-1), or the chemokine KC could be targeted by the steroid to me
diate its antiadhesive effect.
Methods-Rat mesenteries were treated with IL-1 beta (20 ng intraperitoneall
y) and the extent of leucocyte adhesion measured at two and four hours usin
g intravital microscopy. Rats were treated with dexamethasone, and passivel
y immunised against ICAM-1 or KC. Endogenous expression of these two mediat
ors was validated by immunohistochemistry, ELISA, and the injection of spec
ific radiolabelled antibodies.
Results-Dexamethasone greatly reduced IL-1 beta induced leucocyte adhesion,
endothelial expression of ICAM-1 in the postcapillary venule, and release
of the mast cell derived chemokine KC. Injection of specific antibodies to
the latter mediators was also extremely effective in downregulating (>80%)
IL-1 beta induced leucocyte adhesion.
Conclusions-Induction by IL-1 beta of endogenous ICAM-1 and KC contributes
to leucocyte adhesion to inflamed mesenteric vessels. Without excluding oth
er possible mediators, these data clearly show that dexamethasone interfere
s with ICAM-1 expression and KC release from mast cells, resulting in suppr
ession of leucocyte accumulation in the bowel wall, which is a prominent fe
ature of several gastrointestinal pathologies.