title: Review article: thromboxanes in inflammatory bowel disease--pathogenic and therapeutic implications.
abstract: Recent work suggests that thromboxanes may play a major pathogenic role in inflammatory bowel disease. Thromboxanes are produced in excess not only in inflamed mucosa but also in Crohn's disease, by uninflamed bowel and by isolated intestinal and peripheral blood mononuclear cells. Their cellular source is likely to include platelets, neutrophils, endothelial and epithelial cells as well as mononuclear cells, possible stimuli to their overproduction being chemotactic peptides, lipopolysaccharide, leukotrienes, platelet activating factor, interleukin-1, bradykinin and angiotensin II. The pro-inflammatory effects of thromboxanes are both direct (diapedesis and activation of neutrophils, mucosal ulceration, reduction of suppressor T-cell activity) and indirect (vasoconstriction, platelet activation). Although corticosteroids and aminosalicylates inhibit thromboxane synthesis, this action does not necessarily explain their therapeutic effect in inflammatory bowel disease. Selective thromboxane synthesis inhibitors and receptor antagonists, however, ameliorate experimental colitis in animals. Picotamide and ridogrel are dual thromboxane pathway blockers already used in man. Drugs of this type could prove useful not only for the prevention of systemic thrombo-embolism but also for suppressing intestinal mucosal inflammation in patients with inflammatory bowel disease.
authors.affiliation: Gastrointestinal Science Research Unit, London Hospital Medical College, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Rampton
authors.forename: C E
authors.initials: CE
authors.lastname: Collins
mesh_terms: D015777:Eicosanoids / Q000502:physiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D013931:Thromboxanes / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D015777:Eicosanoids; D013931:Thromboxanes