Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drugs (
NSAID) are major pathogenic factors in
peptic ulcer disease but whether these two factors exert synergistic or antagonistic action on the gastric mucosa has been a subject of controversy. The classic concept states that there is an increased
ulcer occurrence and
bleeding in patients with both H. pylori
infection and
NSAID use. However, the question whether the H. pylori eradication
therapy in
NSAID users reduces the occurrence of
peptic ulcer has not been fully addressed. Studies on
secondary prevention of
NSAID-associated
ulcers in H. pylori patients have indicated that H. pylori eradication results in impaired
ulcer healing with an effect on the rate of
peptic ulcer occurrence. On the other hand, the treatment of H. pylori in patients with no prior history of chronic
NSAID therapy has been shown to decrease the risk of
peptic ulcer. Studies in experimental animals revealed for instance, that the H. pylori
infection augments the gastric mucosal damage induced by
NSAID in Mongolian gerbils. In rats with preexisting chromic
gastric ulcers, H. pylori
infection attenuated significantly the
aspirin-induced inhibition of
ulcer healing and accompanying fall in the gastric blood flow at the margin of these
ulcers, suggesting negative interaction between
aspirin and H. pylori on ulcerogenesis. Accumulated evidence in humans and animals shows that both
aspirin and H. pylori upregulate the expression of
cyclooxygenase (COX)-2 both at
mRNA and
protein levels at the
ulcer margin, but failed to influence significantly that of COX-1. It was, therefore, proposed that H. pylori may in fact, antagonize,
aspirin-induced delay of
ulcer healing due to suppression of
acid secretion by the enhancement in
PGE(2) possibly derived from COX-2 expression and activity and to the overexpression of
growth factors such as
TGF alpha and
VEGF. The present review summarizes and further addresses the issue of the interaction between these two major
ulcer risk factors determined in the stomach of humans and experimental animals.