A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection.
A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection.
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IL-12 在血期鼠疟疾致死株伯氏疟原虫 NK65 感染中的致病作用。
DOI：
10.4049/jimmunol.160.11.5500
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发表时间：
1998
影响因子：
4.4
通讯作者：
Hideo Nariuchi
中科院分区：
文献类型：
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作者：
Takayuki Yoshimoto;Yasuhiro Takahama;Chrong;T. Yoneto;S. Waki;Hideo Nariuchi
我们研究了血期鼠疟疾致死性伯氏疟原虫 NK65 的感染是否会诱导 IL-12 的产生，如果是的话，IL-12 的产生如何参与保护或发病机制。 C57BL/6小鼠的感染在感染早期增强了脾脏和肝脏中IL-12 p40以及IFN-γ、IL-4和IL-10的mRNA表达。它还增强了 TNF-α、Fas 配体和细胞因子诱导型一氧化氮合酶的 mRNA 表达。在脾细胞培养上清液和感染小鼠的血清中也观察到 IL-12 p40 产量增加。此外，感染还导致严重肝损伤，血清谷氨酸-草酰乙酸转氨酶和血清谷氨酸-丙酮酸转氨酶活性升高以及体重减轻。用针对IL-12的中和单克隆抗体治疗这些感染的小鼠可延长存活时间并减轻肝损伤，同时降低血清谷氨酸草酰乙酸转氨酶和血清谷氨酸丙酮酸转氨酶活性的升高并减少体重减轻。然而，抗IL-12治疗并没有影响寄生虫血症，所有这些小鼠最终都死亡。当用抗 IFN-γ 的中和单克隆抗体治疗受感染的小鼠时，也获得了类似的结果。此外，抗IL-12治疗大大减少了脾脏和肝脏中IFN-γ的分泌和mRNA表达。这些结果表明致命的伯氏疟原虫NK65感染诱导IL-12的产生，并且IL-12通过IFN-γ的产生而非保护作用参与肝损伤的发病机制。
We studied whether the infection with a blood-stage murine malaria lethal Plasmodium berghei NK65 induces IL-12 production, and if so, how the IL-12 production is involved in the protection or pathogenesis. The infection of C57BL/6 mice enhanced mRNA expression of IL-12 p40 and also IFN-gamma, IL-4, and IL-10 in both spleen and liver during the early course of the infection. It also enhanced the mRNA expression of TNF-alpha, Fas ligand, and cytokine-inducible nitric oxide synthase. Increased IL-12 p40 production was also observed in the culture supernatant of spleen cells and in sera of infected mice. In addition, the infection caused massive liver injury with elevated serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase activities and body weight loss. Treatment of these infected mice with neutralizing mAb against IL-12 prolonged the survival and diminished the liver injury with reduced elevation of serum serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase activities and decreased body weight loss. However, the anti-IL-12 treatment did not affect parasitemia, and all these mice eventually died. Similar results were obtained when infected mice were treated with neutralizing mAb against IFN-gamma. Moreover, anti-IL-12 treatment greatly reduced the secretion and mRNA expression of IFN-gamma in both spleen and liver. These results suggest that the lethal P. berghei NK65 infection induces IL-12 production and that the IL-12 is involved in the pathogenesis of liver injury via IFN-gamma production rather than the protection.
IL-12 对实验性病毒感染的反应和易感性的影响。
DOI：
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发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Orange,JS;Wolf,SF;Biron,CA
通讯作者：
Biron,CA