NEUTROPENIA DOES NOT PREVENT ETODOLAC-INDUCED OR INDOMETHACIN-INDUCEDGASTROINTESTINAL DAMAGE IN THE RAT

Neutrophils have been implicated in the acute formation of gastric muc osal erosions induced by nonsteroidal antiinflammatory drugs. The aims of the present study were to determine, in rats, the role of neutroph ils in the pathogenesis of etodolac- and indomethacin-induced gastroin testinal ulceration and blood loss. Both drugs caused gastrointestinal ulceration, which was associated with increased blood loss, a rise in plasma haptoglobin concentration, and a rise in the number of circula ting neutrophils. A marked infiltration of neutrophils occurred only i n ileal tissue. Pretreatment with a selective antineutrophil serum ind uced a significant neutropenia, which failed to inhibit either etodola c- or indomethacin-induced gastrointestinal ulceration and blood loss. A further study demonstrated that the antineutrophil serum did not pr event gastric erosions induced by indomethacin, but it inhibited carra geenan paw edema, which is dependent, in part, on neutrophil infiltrat ion and activation. It is concluded that neutrophils do not contribute to gastrointestinal ulceration and blood loss induced by nonsteroidal antiinflammatory drugs. Furthermore, in contrast with previous studie s, our results provide no evidence that neutrophils contribute to indo methacin-induced acute gastric erosion formation.