Failure to down-regulate intragraft cytokine mRNA expression shortly after clinical heart transplantation is associated with high incidence of acute rejection.
BACKGROUND
Brain-death, ischemia and reperfusion damage have been implicated as initial factors that lead to a cascade of immunologic events that result in allograft rejection in experimental animals. Cytokines are thought to play a central role in this process. Therefore, we evaluated intragraft cytokine mRNA expression at an early stage after clinical heart transplantation and related these data to ischemia, immunosuppression, and rejection.


METHODS
We sampled endomyocardial biopsies at 30 minutes (EMB 0) and at 1 week (EMB 1) after transplantation from 20 cardiac allograft recipients. Intragraft monocyte chemoattractant protein (MCP-1) and basic fibroblast growth factor (bFGF) mRNA expression levels were quantitatively measured using competitive template Reverse-transcriptase polymerase chain reaction (RT-PCR).


RESULTS
We measured significantly lower MCP-1 and bFGF mRNA expression levels in EMB 1 compared with EMB 0 (MCP-1, p = 0.006; bFGF, p = 0.019). We found no direct correlation between the cytokine mRNA expression levels in EMB 0 or EMB 1 and ischemic times, induction therapy, or cyclosporine whole-blood trough levels. Patients with a high incidence of acute rejection episodes (>2 in the first year) had higher bFGF mRNA expression levels (p = 0.009) and comparable MCP-1 mRNA expression levels (p = 0.378) at 1 week, compared with patients with a lower rejection incidence. The MCP-1 and bFGF mRNA expression levels in the first week were not associated with the development of graft vascular disease in the first year post-transplant.


CONCLUSIONS
We found a significant decrease of intragraft MCP-1 and bFGF mRNA expression levels in the first post-operative week. Patients with a high incidence of acute rejection had higher bFGF mRNA expression levels in their first week biopsy. Therefore, we conclude that patients who fail to down-regulate their bFGF mRNA expression early after transplantation are at higher risk for acute rejection.
de Groot-Kruseman
H A
HA
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands. hadegroot@inw1.azr.nl
Baan
C C
CC
Loonen
E H
EH
Mol
W M
WM
Niesters
H G
HG
Maat
A P
AP
Balk
A H
AH
Weimar
W
W
D000208:Acute Disease; D001706:Biopsy; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics*; D004699:Endocardium / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006084:Graft Rejection / Q000209:etiology* / Q000235:genetics; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007511:Ischemia / Q000150:complications* / Q000235:genetics; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D014652:Vascular Diseases / Q000235:genetics / Q000378:metabolism
D018932:Chemokine CCL2; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D016572:Cyclosporine