salicylates and olsalazine

Aminosalicylates are widely used with azathioprine in the treatment of IBD. The association results in an increase in 6-TGN levels in adults with IBD with a difference in the occurrence of myelotoxic effects. Scarce data are available in pediatric population. We proposed to investigate the effect of the coadministration of aminosalicylates on thiopurine concentrations in pediatric IBD patients.. Data from 71 patients treated for at least 1 y by azathioprine and aminosalicylates were recorded. 6-TGN and 6-MeMPN concentrations, blood cell counts and liver function tests were compared between patients taking and those not taking aminosalicylates.. Aminosalicylate therapy was associated with a significant increase in mean 6-TGN but also 6-MeMPN concentrations. In patients in remission, 6-TGN level was related to aminosalicylate dosage (r = 0.561, p = 0.010). Lymphopenia rate was higher in patients receiving combined therapy compared to monotherapy whereas a slight rise in leucopenia was found.. This observation suggests that the higher frequency of lymphopenia may be associated with the elevated 6-TGN concentrations recovered in patients treated with aminosalicylates. This combination does not improve remission rate but could increase adverse effects especially lymphopenia.

Topics: Adolescent; Aminosalicylic Acids; Azathioprine; Biotransformation; Child; Child, Preschool; Drug Therapy, Combination; Erythrocytes; Female; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphopenia; Male; Mesalamine; Purines; Salicylates; Sulfasalazine

Colonic epithelial cells express HLA-DR in inflammatory bowel disease. The effect of drugs used in the treatment of inflammatory bowel disease and colchicine on interferon-gamma (IFN-gamma) induced DR expression has been investigated. HT-29 cells were cultured in 25 cm2 flasks. At 48 hours interferon-gamma (0, 50, or 100 U/ml) +/- drug were added. At 120 hours the cells were stained for HLA-DR and analysed by flow cytometry. 10(-2) M 5ASA reduced DR expression induced by 50 U/ml interferon-gamma from 62 (12)% of cells (mean SD) to 29 (20)% (p less than 0.005). Corresponding figures for 10(-2) M N-acetyl 5ASA were 68 (16)% to 39 (17)% (p less than 0.05); for 10(-2) M 4ASA, 61 (4)% to 57 (4)% (p = 0.6); for 10(-2) M N-acetyl 4ASA, 60 (12)% to 35 (13)% (p less than 0.05); for 10(-2) M olsalazine, 72 (9)% to 3 (1)% (p less than 0.001); for 10(-3) M olsalazine, 72 (9)% to 16 (10)% (p less than 0.001); for 10(-6) M colchicine, 62 (13)% to 5 (3)% (p less than 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-gamma except with 10(-2) M 4ASA which reduced expression from 77 (4)% to 68 (3)% (p less than 0.05). 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-gamma induced DR expression. 5ASA, N-acetyl 5ASA, 4ASA, N-acetyl 4ASA, olsalazine and colchicine reduce interferon-gamma induced HLA-DR expression. In inflammatory bowel disease these compounds may impair antigen presentation by the colonic epithelium.

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cell Line; Colchicine; Colon; Epithelium; Flow Cytometry; HLA-DR Antigens; Humans; Inflammatory Bowel Diseases; Interferon-gamma; Male; Mesalamine; Middle Aged; Salicylates