Do infiltrating neutrophils contribute to the pathogenesis of indomethacin induced ulceration of the rat gastric antrum?
The potential involvement of neutrophils in the pathogenesis of indomethacin induced ulceration of the gastric antrum in the re-fed rat was studied. Indomethacin was associated with a time dependent increase in the extent and severity of ulceration, blood neutrophilia, neutrophil infiltration into the gastric antrum, and calcium ionophore induced immunoreactive leukotriene B4 (LTB4) release from the antrum ex vivo. Neutrophil infiltration into the antrum was detectable 1 hour after dosing with indomethacin, at which time damage was apparent microscopically but not macroscopically. Thus, cell infiltration may contribute to the development, if not the initiation, of ulceration. Consistent with this suggestion, oral dexamethasone (5 mg/kg) significantly attenuated indomethacin induced ulceration, the associated neutrophil infiltration, and calcium ionophore induced immunoreactive leukotriene B4 release from the gastric antrum and whole blood ex vivo, although the blood neutrophilia was unaffected. These results suggest that indomethacin induced ulceration of the rat gastric antrum may have a dependence on neutrophil infiltration for its pathogenesis.
Department of Gastrointestinal Pharmacology, Glaxo Group Research, Ware, Hertfordshire.
M A
MA
Trevethick
N M
NM
Clayton
P
P
Strong
I W
IW
Harman
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D007213:Indomethacin / Q000009:adverse effects*; D007958:Leukocyte Count / Q000187:drug effects; D007975:Leukotriene B4 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D011706:Pyloric Antrum / Q000473:pathology; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology
D007975:Leukotriene B4; D007213:Indomethacin