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 Ca2+ concentratio n in chronic inflammatory bowel disease, and to ascertain the effect o f anti-inflammatory drugs and other mediators on eicosanoid synthesis and Ca2+ concentration. Methods: Biopsies taken from the descending co lon were isolated biochemically. The suspension of isolated mucosal ce lls was incubated for 15 min in the presence and absence of arachidoni c acid and the Ca2+ ionophore A23187. PGE(2) and LTB(4) concentrations in the incubation medium were measured by radioimmunoassay, and the i ntracellular Ca2+ concentration was determined using fura-2. We studie d 107 subjects. In addition, the effects of bradykinin, endothelin, cy closporin A and PGE(2) on intracellular Ca2+ concentration were determ ined in 25 individuals. Results: untreated patients with active inflam matory bower disease showed a significant increase in LTB(4) synthesis compared with healthy controls. However, in patients receiving steroi ds, sulphasalazine or 5-aminosalicylic acid, both LTB(4) and PGE(2) sy nthesis were markedly decreased. When arachidonic acid was added to th e cell suspension, it significantly stimulated LTB(4) synthesis, espec ially in patients with active disease. Patients with active Crohn's di sease or ulcerative colitis had moderately higher Ca2+ levels than hea lthy controls. However, there was a significant decrease in intracellu lar Ca2+ concentration in patients with quiescent disease who were rec eiving maintenance therapy. Conclusion: We suggest that increased LTB( 4) synthesis and elevated intracellular Ca2+ concentrations contribute to the pathophysiology of inflammatory bowel disease. Drugs effective in the treatment of these diseases may exert their pharmacological ac tion by normalizing these pathological findings.