腸病毒71型感染常在嬰幼兒引起嚴重的神經性症狀，例如腦幹腦炎與類小兒麻痺症。在腸病毒71型感染當中，過度的免疫反應被認為會藉由引起嚴重腦幹腦炎及肺水腫而導致患者死亡，因此建議使用抗發炎製劑，例如類固醇，以壓抑過度的發炎反應及退燒。然而，使用類固醇治療被認為可能加重腸病毒71型感染之病人的病情。因此，類固醇治療對於腸病毒71型感染的影響仍需要被探討。在本篇研究當中，我們以小鼠模式來探究這個議題。我們發現，在感染早期 (感染後第1天) 給予4天或14天類固醇 (dexamethasone, Dex) 治療皆會增加腸病毒71型感染之小鼠的死亡率與後遺症嚴重程度。相較於給予PBS的小鼠，在感染早期給予Dex治療的小鼠其組織中也可偵測到較高的病毒量。Dex具有降低T細胞數量、細胞激素與趨化激素的能力。我們進一步測定的結果顯示，給予Dex治療會降低小鼠的CD4+ T細胞、CD8+ T細胞與CD19+ B細胞的數量，進而導致胸腺和脾臟萎縮。給予Dex治療也會降低腸病毒71型感染之小鼠的IFN-beta產量，但是卻造成IL-6與IP-10產量的增加。除了探討輕量病毒感染的小鼠模式，我們也探討給予Dex治療對高量病毒感染之小鼠的影響，發現在感染早期給予Dex治療也會提高小鼠之死亡率與後遺症嚴重程度。另外，無論是輕量或高量病毒感染之小鼠，在感染後第4或8天給予Dex治療皆不會對小鼠的死亡率造成顯著影響。總括來說，在感染早期給予Dex治療會增加腸病毒71型感染之小鼠的死亡率。我們的結果顯示，類固醇無益於治療腸病毒71型感染，並提供臨床上使用類固醇一個警訊。

Enterovirus 71 (EV71) infection induces severe neurological symptoms, such as encephalitis and poliomyelitis-like paralysis, especially in infants and young children. In EV71 infection, overt immune responses have been suspected to cause death by inducing severe encephalitis and pulmonary edema, so anti-inflammatory agents, such as corticosteroids are recommended to suppress excessive inflammatory responses and reduce fever. However, corticosteroid treatment has been indicated to exacerbate the disease severity of EV71-infected patients. The effects of corticosteroid treatment on EV71 infection remain be examined. In the present study, we used a murine model to investigate the issue. We found that both long term (14-day) and short term (4-day) corticosteroid (dexamethasone, Dex) treatment starting from day 1 post-infection increased the mortality and disease severity of EV71-infected mice. Early Dex treatment increased tissue viral loads. Dex is shown to reduce the levels of T cells, cytokines, and chemokines, so we further quantified these responses. The results showed that Dex treatment caused thymus and spleen atrophy with reductions in the numbers of CD4+ T cells, CD8+ T cells, and CD19+ B cells. Dex treatment also decreased the interferon-beta level, but increased the levels of interleukin-6 and interferon-inducible-protein 10. Besides investigating mice with a low death rate due to a low inoculum dose, we also explored the effects of Dex treatment on mice with a high death rate due to a high inoculum dose and found that early Dex treatment increased the mortality and disease severity of mice. In addition, the mortalities of mice with low or high inoculum dose were not affected by Dex treatment starting from days 4 or 8 post-infection. Collectively, early Dex treatment increases the mortality of EV71 infected-mice. Our results show that corticosteroid treatment has no beneficial effect on EV71 infection and raises the caution over the use of corticosteroids in the clinic.

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