Administration of anti-interleukin-6 monoclonal antibody prolongs cardiac allograft survival.
To investigate the effects of anti-IL-6 monoclonal antibody (anti-IL-6 mAb) on acute allograft rejection and the potential mechanisms in a mouse heart transplantation model. Heterotopical heart graft model was performed. The anti-IL-6 mAb was administered to recipient mice after cardiac grafting. Results were compared with administration of anti-IL-17 mAb or anti-IL-6 mAb+anti-IL-17 mAb (the 'double' treatment). The cardiac allograft survival was monitored by daily palpation in combination with histological evaluation. Quantitative polymerase chain reaction assay, mixed lymphocyte reaction, and flow cytometric analysis were employed to determine the mRNA expression of pro-inflammatory cytokines, allogeneic T-cell proliferation, and the proportion of CD4(+) CD25(+) Foxp3(+) regulatory T cells in graft-infiltrating lymphocytes and splenocytes of recipients, respectively. The results showed that the cardiac allograft survival in anti-IL-6 mAb-treated mice was prolonged significantly when compared with that of the untreated or anti-IL-17 mAb-treated mice. Meanwhile, the 'double-treated' did not prolong graft survival significantly when compared with those treated with anti-IL-6 mAb. The increase of graft survival induced by anti-IL-6 mAb was associated with reduced transcript levels for IFN-γ and IL-17, accompanied by a dramatic reduction of T-cell proliferation capacity to alloantigen stimuli and a higher proportion of Treg cells. Thus, anti-IL-6 mAb may be protective against acute rejection after cardiac transplantation through suppressing the activation of effector T cells and promoting the induction of Treg cells.
Lei
Jun
J
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China.
He
Fan
F
Wu
Min
M
Zheng
Xiang
X
Chen
Xiaoping
X
Chen
Zhishui
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D006084:Graft Rejection / Q000188:drug therapy; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology* / Q000493:pharmacokinetics / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D020381:Interleukin-17; D015850:Interleukin-6