Salicylates for ulcerative colitis--their mode of action.
Delivery of 5-aminosalicylic acid to the colon by sulphasalazine, other azo-bonded compounds and controlled-release preparations is introduced in the context of metabolism by epithelial cells and therapeutic efficacy in ulcerative colitis. Potential modes of action are then reviewed, including actions on luminal bacteria, epithelial cell surface receptors, cellular events (such as nitric oxide release or butyrate oxidation), electrolyte transport and epithelial permeability. Evidence for an influence of salicylates on circulating and lamina propria inflammatory cells is presented, as well as actions on adhesion molecules, chemotactic peptides and inflammatory mediators, such as eicosanoids, platelet-activating factor, cytokines or reactive oxygen metabolites. The precise mechanism will remain uncertain as long as the aetiology of ulcerative colitis is unknown, but a pluripotential mode of action of salicylates is an advantage when influencing the network of events that constitute chronic inflammation.
Travis
S P
SP
Gastroenterology Unit, Derriford Hospital, Plymouth, U.K.
Jewell
D P
DP
D015815:Cell Adhesion Molecules / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003692:Delayed-Action Preparations; D015777:Eicosanoids / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D011355:Prodrugs / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species; D012459:Salicylates / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012460:Sulfasalazine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated
D015815:Cell Adhesion Molecules; D016207:Cytokines; D003692:Delayed-Action Preparations; D015777:Eicosanoids; D011355:Prodrugs; D017382:Reactive Oxygen Species; D012459:Salicylates; D013608:Tablets, Enteric-Coated; D012460:Sulfasalazine