Tumour necrosis factor mediation of nsaid-induced gastric damage:
role of leukocyte adherence.
Appleyard, Caroline B., Donna-Marie McCafferty, Allan W. Tigley, Mark
G. Swain & John L. Wallace.
Intestinal Disease Research Unit, University of Calgary, Calgary,
Alberta, T2N 4N1, Canada
APStracts 2:0159G, 1995.
Neutrophil adherence to the vascular endothelium has been suggested to
be a critical event in the pathogenesis of NSAID-induced gastric
damage. Recently, increased plasma levels of TNF, which can increase
leukocyte adherence, have been reported following administration of
indomethacin. This study was performed to determine the relationship
between plasma TNF levels, leukocyte adherence and NSAID-induced
gastric injury. Administration of indomethacin to rats resulted in a
significant elevation of plasma TNF levels within 30 min, and the
development of gastric erosions. Pretreatment with dexamethasone and
PGE2 almost completely prevented gastric injury and abolished the
rise in plasma TNF. Pentoxifylline dose-dependently reduced both
gastric damage and plasma TNF. Similar effects were observed with
three other TNF synthesis inhibitors, and with an anti-TNF antisera.
Pentoxifylline also significantly reduced the extent of antral
ulceration induced by naproxen. However, pentoxifylline did not
significantly affect indomethacin-induced leukocyte adherence. These
results suggest that TNF plays a critical role in the pathogenesis of
NSAID-induced gastric injury, but this cytokine may not be
responsible for NSAID-induced leukocyte adherence.
Received 3 April 1995; accepted in final form 24 July 1995.
APS Manuscript Number G136-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.