Salicylates used in inflammatory bowel disease and colchicine impair interferon-gamma induced HLA-DR expression.

Abstract

(13)% (p<0.05); for 10-2 M olsalazine, 72 (9)% to 3 (1)% (p<0.001); for 10-3 M olsalazine, 72 (9)% to 16 (10)% (p<0-001); for 10-6 M colchicine, 62 (13)% to 5 (3)% (p<0-001); and for 10-7 M colchicine, 62 (13)% to 10 (3)%. Similar results were obtained when DR was induced by 100 U/ml of interferon-y except with 10-2 M 4ASA which reduced expression from 77 (4)% to 68 (3)% (p<005). Sulphapyridine, prednisolone, indomethacin and cyclosporin A had no effect. Concurrent staining with propidium iodide showed that these results were unchanged when viable cells alone were analysed. Prior incubation of cells with drug, followed by washing, had no effect on interferon-y induced DR expression.

Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

“…The hNAT1/mNAT2 isoform is expressed in a wide range of tissues, including liver, colon, small intestine, placenta, lungs, kidney, bladder, blood, and skin (11,18,32,59). In contrast, hNAT2/mNAT1 is expressed mainly in liver, small intestine, and colon (13,14,29,32,35).…”

“…It also remains unclear whether 5-ASA or its metabolite is an active moiety of therapy. In both cell-free and intact-cell assays, 5-ASA is more potent as an antioxidant than Ac-5-ASA (1,4,26,58), but the two compounds have been reported to have similar potency at inhibiting lipoxygenase (5), eicosanoid production (21), interferon-␥ action (13,14), lipid peroxidation (67), and scavenging HOCl (63). While topical application of Ac-5-ASA to the colon may be of limited or no therapeutic value (61,66), negative findings may be explained by the slow uptake of Ac-5-ASA vs. 5-ASA by colonocytes (37).…”

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

“…Sulfasalazine, the first 5-ASA-containing drug, functions by releasing an active component in the colon through the activity of azo reductase expressed by colonic bacterial. Sulfasalazine has been approved for therapeutic usage because of its ability to improve intestinal mucosal permeability [13,14] . Balsalazine (5-ASA azo bonded to an inert carrier, 4-amino-benzoyl-alanine) can also release 5-ASA through cleavage of the compound by azo reductase expressed by intestinal luminal bacteria.…”

Progress in understanding the mechanisms of action of 5-aminosalicylic acid

“…Reports in the literature evaluating the prevalence of different disease extents may vary for a multitude of reasons, including patient selection bias, differences in methods used to evaluate extent of disease (endoscopy vs radiology), or definition of disease extent. Various studies have found that between 14 and 37% of patients have pancolitis, 36 -41% have disease extending beyond the rectum, and 44 -49% have proctosigmoiditis (3)(4)(5)(6). In contrast, CD can involve any portion of the gastrointestinal tract.…”

“…Sulfasalazine and 5-ASA have been shown to inhibit a number of cell-mediated immune processes in vitro, such as inhibition of both T cell proliferation (3) and the presentation of processed antigen to T cells (4,5). Sulfasalazine and 5-ASA inhibit T cell and natural killer cell cytotoxic effector cells (6 -9).…”