title: Tumor necrosis factor alpha inhibitors as immunomodulatory antirejection agents after intestinal transplantation.
abstract: We reported the successful administration of infliximab for late-onset OKT3-resistant rejection in two patients, who presented persistent ulcerative inflammation of the ileal graft after intestinal transplantation (ITX). Based on this experience, the present study demonstrated our long-term experience with infliximab for different types of rejection-related and inflammatory allograft alterations. Infliximab administration (5 mg/kg body weight (BW)) was initiated at a mean of 18.2 ± 14.1 months after transplantation. The number of administrations per patient averaged 8.4 ± 6.7. Repeat dosing was timed according to clinical signs and graft histology in addition to serum-levels of tumor necrosis factor alpha (TNFα), lipopolysaccharide binding protein (LBP) and C-reactive protein (CRP). Infliximab was successful in the following patients: patients with late-onset OKT3- and steroid-refractory rejection who presented persistent ulcerative alterations of the ileal graft (n = 5), patients with ulcerative ileitis/anastomositis, who did not show typical histological rejection signs (n = 2), and one patient with early-onset OKT3-resistant rejection. Infliximab was not successful in one patient with early-onset OKT3-resistant rejection that was accompanied by treatment-refractory humoral rejection. In conclusion, infliximab can expand therapeutic options for late-onset OKT3- and steroid-refractory rejection and chronic inflammatory graft alterations in intestinal allograft recipients.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité-Universitaetsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: U A
authors.initials: UA
authors.lastname: Gerlach
authors.forename: M
authors.initials: M
authors.lastname: Koch
authors.forename: H-P
authors.initials: HP
authors.lastname: Müller
authors.forename: W
authors.initials: W
authors.lastname: Veltzke-Schlieker
authors.forename: P
authors.initials: P
authors.lastname: Neuhaus
authors.forename: A
authors.initials: A
authors.lastname: Pascher
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001835:Body Weight; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007107:Immune System; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation; D000069285:Infliximab; D007422:Intestines / Q000637:transplantation*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D000069285:Infliximab; D008562:Membrane Glycoproteins; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein