Synergistic effects of RAD and Neoral in inhibition of host-vs.-graft and graft-vs.-host immune responses in rat small-bowel transplantation.
The combined effects of RAD and Neoral were tested in a rat orthotopic small-bowel transplantation model. Seven groups (n = 6) were involved in this study, and each one was included in three rejection models for the evaluation of host-vs.-graft disease (HVG) (LBN-F1 to LEW), graft-vs.-host disease (GVH) (LEW to LBN-F1), and combined HVG and GVH immune responses (BN to LEW). Both drugs were administered orally throughout the study. Low doses of RAD (1.0-2.5 mg/kg/day) combined with Neoral (2.0-5.0 mg/kg/day) produced strong synergistic effects in the prolongation of small-bowel graft survival in HVG (combination index, CI = 0.095, 0.1212), GVH (CI = 0.027, 0.020), and combined HVG and GVH immune responses (CI = 0.070, 0.301). The combination therapy of RAD and Neoral produces a strong synergistic effect toward the inhibition of HVG, GVH, and combined HVG and GVH immune responses in a rat small-bowel transplantation model.
Johnson
Stéphane
S
Laboratory of Experimental Surgery, Research Center of CHUM, Notre-Dame Hospital, University of Montreal, Quebec, Canada.
Qi
Shiji
S
Xu
Dasheng
D
Jolicoeur
Marc
M
Liu
Dingyi
D
Barama
Azemi
A
Busque
Stéphane
S
Smeesters
Christian
C
Daloze
Pierre
P
Chen
Huifang
H
D000284:Administration, Oral; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D004357:Drug Synergism; D000068338:Everolimus; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006789:Host vs Graft Reaction / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D023421:Models, Animal; D016377:Organ Transplantation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000008:administration & dosage* / Q000031:analogs & derivatives
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus