Ulcerative Colitis: Jüngling B

Jüngling B, Kindermann I, Moser C, Püschel W, Ecker KW, Schäfers HJ, Böhm M, Zeuzem S, Giese T, Stallmach A. · Department of Internal Medicine II, Saarland University, Germany. · Z Gastroenterol. · Pubmed #15700214 No free full text.

Abstract: BACKGROUND: Cardiac transplantation has become an accepted treatment modality for end-stage heart failure. Immunosuppressive agents, which are used after transplantation, are considered as therapeutic options for inflammatory bowel disease. CASE REPORT: We report on a 53-year-old patient who was treated for 2 years with cyclosporine A, azathioprine and prednisolone after heart transplantation. He developed a distal colitis with all features of ulcerative colitis. An infectious or ischemic etiology was carefully excluded. In spite of high-dose treatment with prednisolone the patient's abdominal symptoms worsened and he developed a progression of the inflammation in the entire colon and a colectomy with ileostomy was necessary. The histology was consistent with ulcerative colitis. After colectomy he recovered and remained in a good state of health. CONCLUSIONS: This report supports the concept that new onset inflammatory bowel disease can develop in a heart transplantation recipient in spite of immunosuppression.

Pfister K, Wittig BM, Jüngling B, Ecker KW, Barth S, Huhn M, Sasse S, Engert A, Mueller-Molaian I, Diehl V, Zeitz M, Stallmach A. · Department of Internal Medicine II, Saarland University, Homburg/Saar, Germany. · Int J Colorectal Dis. · Pubmed #12014425 No free full text.

Abstract: BACKGROUND AND AIMS: In chronic inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis an aberrant mucosal immune regulation is observed accompanied by upregulation of proinflammatory cytokines. Lamina propria T cells of inflamed mucosa have an activated phenotype characterized by increased expression of surface markers such as CD25. We therefore determined the anti-inflammatory effect of a recombinant immunotoxin consisting of an anti-CD25 single chain variable fragment (scFv) fused to a deletion mutant of Pseudomonas exotoxin A [RFT5(scFv)ETA'] on isolated lamina propria lymphocytes of patients with IBD and in the murine model of trinitrobenzene sulfonic acid (TNBS) induced colitis. PATIENTS AND/METHODS: Lamina propria lymphocytes of 25 patients with IBD and 19 control patients were stimulated in absence or presence of RFT5(scFv)ETA'. Interferon-gamma production was determined in the supernatant by ELISA and the induction of apoptosis by flow cytometry after propidium iodide staining. BALB/c mice received TNBS intrarectally and were treated with RFT5(scFv)ETA'. RESULTS: In vitro the administration of RFT5(scFv)ETA' significantly reduced interferon-gamma production and increased apoptosis in lamina propria lymphocytes isolated of inflamed mucosa. However, this contrainflammatory regulation did not result in gain of weight or increased life span in experimental colitis in vivo. CONCLUSION: In addition to the downregulation of the proinflammatory cytokine in vitro, RFT5(scFv)ETA' induced neither a direct nor a bystander effect in an in vivo model of colitis. Therefore our data do not support potential therapeutic implications of targeting CD25 by RFT5(scFv)ETA' in chronic IBD.