Arachidonic acid metabolism and intracellular calcium concentration in inflammatory bowel disease

Objective: To study the alteration of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) synthesis and intracellular Ca 2+ concentration in chronic inflammatory bowel disease, and to ascertain the effect of anti-inflammatory drugs and other mediators on eicosanoid synthesis and Ca 2+ concentration. Methods: Biopsies taken from the descending colon were isolated biochemically. The suspension of isolated mucosal cells was incubated for 15 min in the presence and absence of arachidonic acid and the Ca 2+ ionophore A23187. PGE 2 and LTB 4 concentrations in the incubation medium were measured by radioimmunoassay, and the intracellular Ca 2+ concentration was determined using fura-2. We studied 107 subjects. In addition, the effects of bradykinin, endothelin, cyclosporin A and PGE 2 on intracellular Ca 2+ concentration were determined in 25 individuals. Results: Untreated patients with active inflammatory bowel disease showed a significant increase in LTB 4 synthesis compared with healthy controls. However, in patients receiving steroids, sulphasalazine or 5-aminosalicylic acid, both LTB 4 and PGE 2 synthesis were markedly decreased. When arachidonic acid was added to the cell suspension, it significantly stimulated LTB 4 synthesis, especially in patients with active disease. Patients with active Crohn's disease or ulcerative colitis had moderately higher Ca 2+ levels than healthy controls. However, there was a significant decrease in intracellular Ca 2+ concentration in patients with quiescent disease who were receiving maintenance therapy. Conclusion: We suggest that increased LTB 4 synthesis and elevated intracellular Ca 2+ concentrations contribute to the pathophysiology of inflammatory bowel disease. Drugs effective in the treatment of these diseases may exert their pharmacological action by normalizing these pathological findings.