Sadeghi Mahmoud, Daniel Volker, Naujokat Cord, Schnitzler Paul, Schmidt Jan, Mehrabi Arianeb, Zeier Martin, Opelz Gerhard
Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany.
Transplantation. 2008 Jul 27;86(2):275-85. doi: 10.1097/TP.0b013e31817b063d.
Pre- and posttransplant predisposing factors for cytomegalovirus (CMV) activation and disease are not well defined. The aim of this study was to examine whether there are differences in plasma cytokine levels pretransplant, before and during CMV replication in renal transplant recipients.
We studied 76 renal transplant recipients in whom CMV-DNA was studied at regular intervals posttransplant. Thirty-eight patients developed CMV viremia posttransplant (CMV-DNA-positive). Thirty-eight patients had no detectable CMV-DNA posttransplant (CMV-DNA-negative). Cytokine and cytokine receptors/antagonists plasma levels were measured pretransplant, and pre-, during, and after CMV-viremia in CMV-DNA-positive patients and at similar time points in CMV-DNA-negative transplant recipients.
Compared with pretransplant, after transplantation soluble (s) plasma interleukin (IL)-2 receptor (R), IL-6, and interferon-gamma (IFN-gamma) decreased in both groups (CMV-DNA-positive: P=0.002; P=0.028; P=0.032; CMV-DNA-negative: P=0.001; P=0.040; P=0.030) whereas IL-10 remained constant in both groups (P=n.s.). During CMV viremia, sIL-2R (P=0.015) and IL-6 (P=0.006) increased compared with previremia but remained constant in CMV-DNA-negative patients matched for the day of investigation (P=n.s.). Simultaneously, IFN-gamma increased in CMV-DNA-negative patients (P=0.008) and remained constant in CMV-DNA-positive patients (P=n.s.). During CMV viremia, IL-10 (P=0.002) and sIL-2R (P=0.007) were significantly higher in CMV-DNA-positive than CMV-DNA-negative patients investigated at similar time points.
Our results indicate that CMV replication in renal transplant recipients is associated with increased sIL-2R, IL-6, and IL-10 and decreased IFN-gamma plasma levels, pointing to a monocyte/Th2 activation and a Th1 blockade. The high IL-10 might decrease the IFN-gamma plasma levels in CMV-DNA-positive patients. Th1 deficiency in CMV-DNA-positive patients might promote development of CMV disease.
移植前后巨细胞病毒（CMV）激活及发病的易感因素尚不明确。本研究旨在探讨肾移植受者移植前、CMV复制前及复制期间血浆细胞因子水平是否存在差异。
我们研究了76例肾移植受者，在移植后定期检测其CMV-DNA。38例患者移植后发生CMV病毒血症（CMV-DNA阳性）。38例患者移植后未检测到CMV-DNA（CMV-DNA阴性）。在移植前、CMV-DNA阳性患者发生CMV病毒血症前、期间及之后，以及在CMV-DNA阴性移植受者的相似时间点，测量血浆细胞因子及细胞因子受体/拮抗剂水平。
与移植前相比，移植后两组可溶性（s）血浆白细胞介素（IL）-2受体（R）、IL-6和干扰素-γ（IFN-γ）均降低（CMV-DNA阳性组：P = 0.002；P = 0.028；P = 0.032；CMV-DNA阴性组：P = 0.001；P = 0.040；P = 0.030），而两组IL-10水平保持恒定（P = 无显著差异）。在CMV病毒血症期间，与病毒血症前相比，sIL-2R（P = 0.015）和IL-6（P = 0.006）升高，但在调查当天匹配的CMV-DNA阴性患者中保持恒定（P = 无显著差异）。同时，CMV-DNA阴性患者的IFN-γ升高（P = 0.008），而CMV-DNA阳性患者保持恒定（P = 无显著差异）。在CMV病毒血症期间，在相似时间点进行调查的CMV-DNA阳性患者的IL-10（P = 0.002）和sIL-2R（P = 0.007）显著高于CMV-DNA阴性患者。
我们的结果表明，肾移植受者中的CMV复制与sIL-2R、IL-6和IL-10升高以及血浆IFN-γ水平降低有关，提示单核细胞/Th2激活和Th1阻断。高IL-10可能会降低CMV-DNA阳性患者的血浆IFN-γ水平。CMV-DNA阳性患者的Th1缺乏可能促进CMV疾病的发展。
