Acute gastric mucosal injury associated with the systemic administration of interleukin-4

Seventy-three patients with advanced malignancy were treated with the recombinant lymphokine interleukin-4 either as the sole immunotherapeutic reagent or in combination with recombinant interleukin-2.

Twelve of 84 courses of therapy were complicated by gastroduodenal erosion or ulceration. Three of these courses were associated with significant bleeding, which required multiple red blood cell transfusions and endoscopic therapy. No treatment-related deaths occurred. Eleven of 57 courses administered with concomitant indomethacin and 11 of 62 courses administered with ranitidine resulted in gastroduodenal mucosal injury. No acute change in gastric acid output occurred after one dose of interleukin-4 in patients prospectively evaluated with an indwelling nasogastric tube. An intravenous ranitidine infusion appropriately reduced acid output in these patients. In contrast, we have treated over 650 patients with interleukin-2 and indomethacin without interleukin-4, none of whom developed signs or symptoms of gastroduodenal ulceration.

These observations suggest that systemically administered cytokines may exert an effect on the integrity of the gastroduodenal mucosa.