title: Effect of cyclosporine in a murine model of experimental colitis.
abstract: The use of immunosuppressive therapy may be associated with significant toxicity. The aim of this study was to investigate the effect of cyclosporine A (CsA) in murine model of experimental colitis. Experimental colitis was induced in NMRI mice using an enema of 0.2% solution of dinitrofluorobenzene, combined with skin sensitization. After inducing colitis, experimental groups of animals were treated with CsA (1, 3, 5, 10, 25, 50 mg/kg/day) intraperitoneally (i.p.) or intracolonically (i.c.), and control groups were treated with phosphate-buffered saline intraperitoneally or intracolonically, respectively. Colonic inflammatory changes were assessed using a histopathologic score of 0-30, and pooled whole blood samples were processed with monoclonal antibodies for cyclosporine concentration. In addition, two groups of animals with experimental colitis were treated intraperitoneally or intracolonically with 3 mg/kg/day of CsA, and the colons were also taken for immunohistochemistry for CD25. CsA diminished the extent of colitis in groups treated with 3, 5, 10, or 25 mg/kg intraperitoneally or intracolonically, and in groups treated with 1 and 50 mg/kg intracolonically (P < 0.05). The effect of intracolonic application of CsA was not related to whole blood cyclosporine concentrations. In addition, the effect of CsA at 3 mg/kg, applied intraperitoneally or intracolonically was, in part, expressed in decreasing the numbers of CD25+ cells within colonic mucosa/submucosa (P < 0.05). In conclusions, the results of this study indicate the possibility of intracolonic application of cyclosporine in order to widen the therapeutic window for effective, but possibly toxic drug, such as cyclosporine.
authors.affiliation: Division of Gastroenterology, University Hospital Dubrava, Zagreb, Croatia.
authors.forename: Marko
authors.initials: M
authors.lastname: Banić
authors.forename: Branimir
authors.initials: B
authors.lastname: Anić
authors.forename: Tomislav
authors.initials: T
authors.lastname: Brkić
authors.forename: Neven
authors.initials: N
authors.lastname: Ljubicić
authors.forename: Sanja
authors.initials: S
authors.lastname: Plesko
authors.forename: Csaba
authors.initials: C
authors.lastname: Dohoczky
authors.forename: Damir
authors.initials: D
authors.lastname: Erceg
authors.forename: Mladen
authors.initials: M
authors.lastname: Petrovecki
authors.forename: Igor
authors.initials: I
authors.lastname: Stipancić
authors.forename: Ivo
authors.initials: I
authors.lastname: Rotkvić
mesh_terms: D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine