腸病毒七十一型感染常在幼兒引發重症，症狀包括無菌性腦膜炎、腦幹腦炎以及急性肢體麻痺，並伴隨肺水腫及心肺衰竭等併發症，嚴重可致死。在腦幹腦炎的病人血液裡可以測到許多細胞激素表現量的增加，而在動物模式的研究當中證明細胞激素可以調控腸病毒七十一型造成的疾病之嚴重度。介白素-19與20與許多過度發炎的疾病有關，像是牛皮癬與類風溼性關節炎，但是很少人去探討介白素-19與20在腸病毒七十一型感染中的重要性。我們首先測量腸病毒七十一型感染的老鼠當中的介白素-19與20，發現感染腸病毒七十一型會使老鼠腦部與血清中的介白素-19顯著地增加，但介白素-20並沒有明顯地增加。另外，我們也發現介白素-19是由神經細胞所表現。先前已知介白素-19可以透過第一型介白素-20受體(由IL-20R1與IL-20R2所組成)傳訊，因此我們接著去看IL-20R1在腸病毒七十一型感染鼠腦中的表現，結果發現腸病毒七十一型感染顯著地增加鼠腦中的IL-20R1表現量，除此之外，我們也發現IL-20R1是由神經細胞表現。之後，我們利用IL-20R1的基因缺陷鼠，更進一步探討介白素-19在感染所扮演的角色。結果顯示感染之後，基因缺陷鼠的死亡率低於野生型鼠46%，此外，基因缺陷鼠在中樞神經系統的病毒量也顯著低於野生型鼠。以前研究證實介白素-19可以調控許多發炎相關的細胞激素，而研究結果發現基因缺陷鼠腦中的介白素-1β在未感染與感染後都顯著地低於野生型鼠。接著我們也去測試基因缺陷鼠感染腸病毒七十一型後是否會影響白血球浸潤。結果發現基因缺陷鼠脾臟中的CD19+ B細胞以及鼠腦中的CD4+的細胞顯著地低於野生型鼠。綜合以上的結果，腸病毒七十一型感染後，鼠腦與血液中的介白素-19以及鼠腦中的IL-20R1顯著地增加。另外，在缺乏IL-20R1的情況下會增加腸病毒七十一型感染老鼠的存活率並且減少中樞神經系統中的病毒量。

Enterovirus 71 (EV71) has induced fatal encephalitis in thousands of young children in the Asia-Pacific region since the past decade. Cytokines are elevated in infected patients with brainstem encephalitis. Mouse studies show that cytokines can regulate the severity of EV71-induced disease. Cytokines, IL-19 and IL-20 are shown to be associated with overwhelming inflammatory diseases, such as psoriasis and rheumatoid arthritis. Few studies have investigated the induction and importance of these cytokines in EV71 infection. We first determined IL-19 and IL-20 levels in EV71-infected mice and found that EV71 infection significantly enhanced the levels of IL-19, but not IL-20, in the mouse brain and serum. IL-19 was expressed in the brain neuron. IL-19 is the ligand of type I IL-20 receptor complex that is comprised of IL-20R1 and IL-20R2. We examined and found that EV71 infection significantly increased the mouse brain level of IL-20R1 which was expressed in the brain neuron. Moreover, we found that after EV71 infection, the survival rate of IL-20R1 knockout mice was significantly higher than that of wild-type mice by 46%. In addition, the mean viral titers in the central nervous system of IL-20R1 knockout mice were significantly lower than those of wild-type mice. Furthermore, we found that absence of IL-20R1 affected cytokine expression with decreases in the brain IL-1β levels of both mock-infected and infected mice. Our findings also showed that IL-20R1 deficiency significantly decreased CD19+ B cells in the infected mouse spleen and CD4+ cells in the infected mouse brain. These results collectively show that type I IL-20 receptor affects the disease progression of EV71-infected mice.

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