Baan C C, Niesters H G, Balk A H, Mochtar B, Zondervan P E, Weimar W
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
J Heart Lung Transplant. 1996 Dec;15(12):1184-93.
We studied the effect of antirejection therapy on intragraft cytokine mRNA expression.
Therapy consisted of three doses of 1 gm of intravenous methylprednisolone. We determined its effect on intragraft mRNA expression of immunoregulatory (interleukin-2, interleukin-4) and inflammatory cytokines (interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha), and the high-affinity interleukin-2 receptor (p55 chain) in endomyocardial biopsy specimens from cardiac allograft recipients.
By reverse-transcriptase polymerase chain reaction methods, we detected mRNA transcription for interleukin-2 in 56% of the pretreatment endomyocardial biopsy specimens (n = 16), for interleukin-4 in 31%, and for interleukin-6 in 56% of the specimens, and interleukin-2 receptor, interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha were constitutively expressed. Individual cytokine mRNA profiles were not helpful in differentiating between rejections that proved to be methylprednisolone resistant (n = 9) or methylprednisolone sensitive (n = 7). After successful antirejection therapy, the overall intragraft mRNA expression was downregulated. None of the posttreatment endomyocardial biopsy specimens taken from six patients with methylprednisolone-sensitive rejections expressed the interleukin-2 gene, in contrast to 88% of the endomyocardial biopsy specimens obtained from eight patients with methylprednisolone-resistant rejections (p = 0.005). Moreover, intragraft interleukin-4 and interleukin-6 mRNA transcripts were hardly detectable (both 17%) in methylprednisolone-reversible rejections, but in ongoing rejections interleukin-4 mRNA expression was found in 62% (p = 0.14), and interleukin-6 was found in 88% of the endomyocardial biopsy specimens (p = 0.03). Semiquantitative analysis showed that the intragraft interleukin-2 receptor, interleukin-1 beta, and tumor necrosis factor-alpha mRNA levels were lower in posttreatment endomyocardial biopsy specimens from methylprednisolone-reversible rejections than in endomyocardial biopsy specimens from methylprednisolone-irreversible rejections (p = 0.03).
Our data suggest that the efficacy of antirejection therapy with methylprednisolone is reflected in intragraft cytokine mRNA profiles.
我们研究了抗排斥治疗对移植组织内细胞因子mRNA表达的影响。
治疗方案为静脉注射3剂1克甲泼尼龙。我们测定了其对心脏移植受者心内膜活检标本中免疫调节细胞因子（白细胞介素-2、白细胞介素-4）、炎性细胞因子（白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α）以及高亲和力白细胞介素-2受体（p55链）的移植组织内mRNA表达的影响。
通过逆转录聚合酶链反应方法，我们在56%的预处理心内膜活检标本（n = 16）中检测到白细胞介素-2的mRNA转录，在31%的标本中检测到白细胞介素-4的mRNA转录，在56%的标本中检测到白细胞介素-6的mRNA转录，并且白细胞介素-2受体、白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α呈组成性表达。个体细胞因子mRNA谱无助于区分对甲泼尼龙耐药的排斥反应（n = 9）和对甲泼尼龙敏感的排斥反应（n = 7）。抗排斥治疗成功后，移植组织内的总体mRNA表达下调。在6例对甲泼尼龙敏感的排斥反应患者的治疗后心内膜活检标本中，无一表达白细胞介素-2基因，相比之下，在8例对甲泼尼龙耐药患者的心内膜活检标本中，88%表达该基因（p = 0.005）。此外，在甲泼尼龙可逆转的排斥反应中，移植组织内白细胞介素-4和白细胞介素-6的mRNA转录本几乎检测不到（均为17%），但在持续的排斥反应中，62%的心内膜活检标本中发现白细胞介素-4的mRNA表达（p = 0.14），88%的心内膜活检标本中发现白细胞介素-6的mRNA表达（p = 0.03）。半定量分析表明，甲泼尼龙可逆转的排斥反应患者治疗后心内膜活检标本中移植组织内白细胞介素-2受体、白细胞介素-1β和肿瘤坏死因子-α的mRNA水平低于甲泼尼龙不可逆转的排斥反应患者的心内膜活检标本（p = 0.03）。
我们的数据表明，甲泼尼龙抗排斥治疗的疗效反映在移植组织内细胞因子mRNA谱中。
