Picotamide inhibition of excess in vitro thromboxane B-2 release by colorectal mucosa in inflammatory bowel disease

Background: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A(2) has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. Methods: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B-2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. Results: Increased amounts of thromboxane B-2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147-325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61-140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64-206), 8). Incubation with picotamide at concentrations between 100 mu M and 1 mM reduced thromboxane B-2 release (IC50 890 mu M). Conclusion: Since increased thromboxane A(2) production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.