Schmidtke M, Glück B, Merkle I, Hofmann P, Stelzner A, Gemsa D
Institute of Virology at the Medical Center of the Friedrich Schiller University, Jena, Germany.
J Med Virol. 2000 Aug;61(4):518-26.
Since cytokines play an important role in the pathogenesis of virus-induced chronic heart diseases, cytokine mRNA expression was studied in coxsackievirus B3-infected NMRI mice during the acute phase of myocarditis until the onset of chronic cardiac disease. Virus replication, cytokine induction, inflammatory cell infiltration and myocardial damage were studied by titer determination, reverse transcription-polymerase chain reaction (RT-PCR), and histopathology. To investigate whether the coxsackievirus B3-induced cytokine mRNA accumulation was only limited to the heart or generalized, spleen and thymus specimens were also included. Surprisingly, interleukin (IL)-10 as a deactivator of T cell and macrophage functions was transcribed in the myocardium nearly in parallel with virus replication from Day 1 through Day 14. At Day 3 p.i., the mRNA of IL-1alpha, tumor necrosis factor (TNF)-alpha, IL-6, and interferon (IFN)-beta accumulated. At Days 4, 7, and 14, IL-12-specific mRNA was produced. Furthermore, increasing amounts of IFN-gamma mRNA were found, whereas IL-2 and IL-4 mRNA remained undetectable. TNF-alpha, IL-1alpha, IL-10, IL-12, and IFN-gamma mRNA persisted into the late stage of myocarditis. In the spleen a closely correlated expression of virus and IL-10-specific mRNAs was also found, and in addition, IFN-beta, TNF-alpha, and IL-6 were detected. In striking contrast to heart and spleen tissue, the distinct expression of viral RNA in the thymus was not accompanied by an increased cytokine mRNA production. These data provide evidence for a unique coxsackievirus B3-induced cytokine pattern in the myocardium and spleen and suggest that persistently expressed IL-10 may play a leading role in acute and chronic myocarditis by subverting the immune response.
由于细胞因子在病毒诱导的慢性心脏病发病机制中起重要作用，因此在柯萨奇病毒B3感染的NMRI小鼠中，研究了从心肌炎急性期直至慢性心脏病发作期间细胞因子mRNA的表达情况。通过滴度测定、逆转录聚合酶链反应（RT-PCR）和组织病理学研究了病毒复制、细胞因子诱导、炎性细胞浸润和心肌损伤情况。为了研究柯萨奇病毒B3诱导的细胞因子mRNA积累是否仅局限于心脏还是全身性的，还纳入了脾脏和胸腺标本。令人惊讶的是，作为T细胞和巨噬细胞功能失活剂的白细胞介素（IL）-10，从第1天到第14天在心肌中的转录几乎与病毒复制同步。感染后第3天，IL-1α、肿瘤坏死因子（TNF）-α、IL-6和干扰素（IFN）-β的mRNA积累。在第4、7和14天，产生了IL-12特异性mRNA。此外，发现IFN-γ mRNA的量增加，而IL-2和IL-4 mRNA仍未检测到。TNF-α、IL-1α、IL-10、IL-12和IFN-γ mRNA持续到心肌炎后期。在脾脏中也发现病毒和IL-10特异性mRNA密切相关的表达，此外，还检测到IFN-β、TNF-α和IL-6。与心脏和脾脏组织形成鲜明对比的是，胸腺中病毒RNA的明显表达并未伴随着细胞因子mRNA产量的增加。这些数据为柯萨奇病毒B3在心肌和脾脏中诱导的独特细胞因子模式提供了证据，并表明持续表达的IL-10可能通过颠覆免疫反应在急性和慢性心肌炎中起主导作用。
