[Effect of mono and combination therapy with FTY720 and ICAM-1 mAb for mouse-to-rat cardiac xenotransplantation].
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).


CONCLUSIONS
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.
Xiong
Hai-Bo
HB
Institute of Transplantation, Third Xiangya Hospital, Central South University, Changsha 410013, China. haiboxiong@sohu.com
Huang
Zu-Fa
ZF
Ye
Qi-Fa
QF
Xia
Sui-Sheng
SS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods*; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011409:Propylene Glycols; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007371:Interferon-gamma; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine