Failure to down-regulate intragraft cytokine mRNA expression shortly afterclinical heart transplantation is associated with high incidence of acute rejection

Background: Brain-death, ischemia and reperfusion damage have been implicat ed as initial factors that lead to a cascade of immunologic events that res ult in allograft rejection in experimental animals. Cytokines are thought t o play a central role in this process. Therefore,, we evaluated intragraft cytokine mRNA expression at an early stage after clinical heart transplanta tion 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. In tragraft monocyte chemoattractant protein (MCP-1) and basic fibroblast grow th factor (bFGF) mRNA expression levels were quantitatively measured using competitive template Reverse-transcriptase polymerase chain reaction (RT-PC R). Results: We measured significantly lower MCP-1 and bFGF mRNA expression lev els in EMB 1 compared with EMB 0 (MCP-1, p = 0.006; bFGF, p = 0.019). We fo und no direct correlation between the cytokine mRNA expression levels in EM B 0 or EMB 1 and ischemic times, induction therapy, or cyclosporine whole-b lood trough levels. Patients with a high incidence of acute rejection episo des (>2 in the first year) had higher bFGF mRNA expression levels (p = 0.00 9) and comparable MCP-1 mRNA expression levels (p = 0.378) at 1 week, compa red with patients with a lower rejection incidence. The MCP-1 and bFGF mRNA expression levels in the first week were not associated with the developme nt of graft vascular disease in the first year post-transplant. Conclusions: We found a significant decrease of intragraft MCP-1 and bFGF m RNA expression levels in the first post-operative week. Patients with a hig h incidence of acute rejection had higher bFGF mRNA expression levels in th eir first week biopsy. Therefore, we conclude that patients who fail to dow n-regulate their bFGF mRNA expression early after transplantation are at hi gher risk for acute rejection.