Article Text
Abstract
BACKGROUND A previous study showed that the glucocorticoid dexamethasone, at doses of 100 μg/kg and above, inhibited leucocyte adhesion to rat mesenteric postcapillary venules activated with interleukin 1β (IL-1β), as assessed by videomicroscopy.
AIMS To identify whether the adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), or the chemokine KC could be targeted by the steroid to mediate its antiadhesive effect.
METHODS Rat mesenteries were treated with IL-1β (20 ng intraperitoneally) and the extent of leucocyte adhesion measured at two and four hours using intravital microscopy. Rats were treated with dexamethasone, and passively immunised against ICAM-1 or KC. Endogenous expression of these two mediators was validated by immunohistochemistry, ELISA, and the injection of specific radiolabelled antibodies.
RESULTS Dexamethasone greatly reduced IL-1β 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-1β induced leucocyte adhesion.
CONCLUSIONS Induction by IL-1β of endogenous ICAM-1 and KC contributes to leucocyte adhesion to inflamed mesenteric vessels. Without excluding other possible mediators, these data clearly show that dexamethasone interferes with ICAM-1 expression and KC release from mast cells, resulting in suppression of leucocyte accumulation in the bowel wall, which is a prominent feature of several gastrointestinal pathologies.
- inflammation
- glucocorticoids
- intravital microscopy
- mast cell
- neutrophil
- endothelium
Abbreviations used in this paper
- BSA
- bovine serum albumin
- DEX
- dexamethasone
- ICAM
- intercellular adhesion molecule
- IL
- interleukin
- PBS
- phosphate buffered saline
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Abbreviations used in this paper
- BSA
- bovine serum albumin
- DEX
- dexamethasone
- ICAM
- intercellular adhesion molecule
- IL
- interleukin
- PBS
- phosphate buffered saline