Effect of mono and combination therapy with FTY720 and ICAM-1 mAb for mouse-to-rat cardiac xenotransplantation.
- Author:
Hai-Bo XIONG
1
;
Zu-Fa HUANG
;
Qi-Fa YE
;
Sui-Sheng XIA
Author Information
1. Institute of Transplantation, Third Xiangya Hospital, Central South University, Changsha 410013, China. haiboxiong@sohu.com
- Publication Type:Journal Article
- MeSH:
Animals;
Antibodies, Monoclonal;
therapeutic use;
Dose-Response Relationship, Drug;
Drug Therapy, Combination;
Female;
Fingolimod Hydrochloride;
Graft Rejection;
blood;
etiology;
prevention & control;
Graft Survival;
drug effects;
Heart Transplantation;
adverse effects;
methods;
Immunoglobulin M;
blood;
Immunosuppressive Agents;
therapeutic use;
Intercellular Adhesion Molecule-1;
immunology;
Interferon-gamma;
blood;
Interleukin-2;
blood;
Interleukin-4;
blood;
Mice;
Mice, Inbred BALB C;
Propylene Glycols;
therapeutic use;
Rats;
Rats, Wistar;
Sphingosine;
analogs & derivatives;
therapeutic use;
Time Factors;
Transplantation, Heterologous
- From:
Journal of Central South University(Medical Sciences)
2007;32(1):41-46
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To observe the effect of FTY720 and ICAM-1 mAb mono and combination therapy in mouse-to-rat cardiac xenotransplantation.
METHODS:Cardiac xenotransplantation was performed in abdominal site with micro-surgical technique. Recipients with xenografts were treated with different doses of FTY720 and/or ICAM-1 mAb. Graft survival, histopathology, infiltration of CD4+, and CD8+ T cells and levels of serum IL-2, IFN-gamma, IL-4, and IgM were investigated.
RESULTS:Survival time of xenografts was (2.75+/- 0.43)d in the controls, survival of grafts treated with ICAM-1 mAb did not significantly improve. Treatment with large dose FTY720 led to a survival of (4.25+/- 0.71)d (P<0.01). Combination therapy with large dose FTY720 and ICAM-1 mAb achieved a significant prolongation of graft survival with (10.25+/- 2.12)d (P<0.01). Levels of serum IL-2, IFN-gamma and rat-anti-mouse IgM decreased in the combined therapy group. Pathologic lesion and infiltration of T cells in xenografts showed mitigated in the large dose combined therapy group. There was a significant negative correlation between the antibody level and the graft survival time (R=-0.754, P<0.01).
CONCLUSION:The combined therapy of FTY720 and ICAM-1 mAb can achieve a significant effect in the prolongation of heart xenograft survival and inhibition of xenoantibodies.
