Effect of cyclosporine in a murine model of experimental colitis.
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.
Banić
Marko
M
Division of Gastroenterology, University Hospital Dubrava, Zagreb, Croatia.
Anić
Branimir
B
Brkić
Tomislav
T
Ljubicić
Neven
N
Plesko
Sanja
S
Dohoczky
Csaba
C
Erceg
Damir
D
Petrovecki
Mladen
M
Stipancić
Igor
I
Rotkvić
Ivo
I
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
D007166:Immunosuppressive Agents; D016572:Cyclosporine