Anti-CD25 monoclonal antibody modulates cytokine expression and prolongs allografts survival in rats cardiac transplantation.
OBJECTIVE
To investigate the role of anti- interleukin-2 receptor (CD25) monoclonal antibody in the regulation of cytokine mRNA expression of IL-1beta, IL-2, CD25, IL-4, IL-5, IL-6, IL-10, tumour necrosis factor-alpha (TNFalpha), and interferon-gamma (IFNgamma) in cardiac allografts to elucidate its immunological mechanism and role in rats that have undergone cardiac transplantation.


METHODS
These in vivo studies were conducted using a rat MHC mismatch SD to Wistar heterotopic cardiac transplant model. Simulect, an anti-CD25 antibody, was used to prevent allograft rejection. An increase in the rate of allograft survival was observed. Rats were sacrificed on day 1, 3, 5, 7, 9, 11, 14 post-transplantation and hearts were harvested for further study. Cytokine mRNA expression was determined by semiquantitative RT-PCR.


RESULTS
In the control group, cardiac allografts were rejected at 8.3 +/- 1.7 days after transplantation (x +/- s). The rats who received CsA rejected the cardiac allograft at 26.4 +/- 5.7 days post-transplant. Allograft survival of Simulect-treated rats was 29.2 +/- 7.1 days (P < 0.05 vs controls). Rats treated with simulect and CsA had the longest survival of 55.0 +/- 11.6 days (P < 0.001 vs controls). CD25 mRNA expression in the heart tissue samples of treated rats was undetectable or very weak. However, the untreated group, CD25 expression increased, although anti-CD25 decreased this CD25 expression in the heart graft. Furthermore, in untreated allografts, IL-2, TNFalpha and IFN-gamma were strongly expressed, an effect that markedly decreased after simulect treatment. Finally, IL-4, IL-5, IL-6 and IL-10 expression was strong in anti-CD25-treated allografts.


CONCLUSIONS
These results suggest that anti-CD25 antibody treatment may not only neutralize CD25 activity but also play a role in altering cytokine mRNA expression and prolong the survival of allografts.
Xia
Jiahong
J
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. xiajiahong@hotmail.com
Jiang
Xionggang
X
Huang
Yi
Y
Zhang
Kailun
K
Xiao
Shiliang
S
Yang
Chenyuan
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D016207:Cytokines; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2