EICOSANOID SYNTHESIS IN DUODENAL-ULCER DISEASE - DECREASE IN LEUKOTRIENE-C4 BY COLLOIDAL BISMUTH SUBCITRATE

The release of immunoreactive prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) from antral and duodenal mucosal biopsy specimens taken from 20 patients with duodenal ulcer disease was measured by radioimmunoassay before and four weeks after treatment with colloidal bismuth subcitrate. Gastroscopic and histological examination showed complete ulcer healing in 15/18 patients and duodenal histology looked normal (n = 15) or improved (n = 3): two patients failed to attend for a second endoscopy. Analysis of the supernatant from incubations of biopsy tissue in vitro showed that unstimulated antral release of PGE2 was significantly more than that from the duodenal mucosa (p < 0.05), whereas basal release of LTC4 was significantly lower from antral biopsy specimens (p < 0.05). Subsequent incubation of specimens with calcium ionophore A23187 caused an increase in LTC4 but not in PGE2 generation. The ability of antral and duodenal mucosa to form ionophore mediated LTC4 in patients with duodenal ulcer disease was significantly greater (p < 0.05; p < 0.01 respectively) than that of normal gastroduodenal mucosa. After colloidal bismuth subcitrate treatment, basal synthesis of PGE2 was unchanged in duodenal and antral specimens. In contrast, basal duodenal LTC4 was reduced (p < 0.05), and the capacity for ionophore mediated duodenal LTC4 formation was substantially and significantly reduced after treatment (p < 0.001). These results indicate that after therapeutic healing of duodenal ulcer (accompanied by clearance of inflammatory cell infiltrate), there is a reduced ability of duodenal mucosa to generate proinflammatory peptidoleukotrienes.