Mice infected with mouse hepatitis virus A59 (MHV-A59) develop hepatitis and autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH), a fact closely related to the release of alarmins such as uric acid and/or high-mobility group box protein 1 (HMGB1). We studied the effect of neutralizing monoclonal antibodies (MAb) against IL-17A in our model of mouse MHV-A59-infection. MAb anti-IL-17F and anti-IFNγ were used to complement the study. Results showed that transaminase levels markedly decreased in MHV-A59-infected mice treated with MAb anti-IL-17A whereas plasmatic Ig concentration sharply increased. Conversely, MAb anti-IL-17F enhanced transaminase liberation and did not affect Ig levels. Serum IFNγ was detected in mice infected with MHV-A59 and its concentration increased after MAb anti-IL-17A administration. Besides, MAb anti-IFNγ greatly augmented transaminase plasmatic levels. IL-17A neutralization did not affect MHV-A59-induction of HMGB1 liberation and slightly augmented plasmatic uric acid concentration. However, mice treated with the MAb failed to produce autoAb to FAH. The above results suggest a reciprocal regulation of Th1 and Th17 cells acting on the different MHV-A59 effects. In addition, it is proposed that IL-17A is involved in alarmins adjuvant effects leading to autoAb expression.

中文翻译：

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白介素17A（IL-17A）中和对鼠肝炎病毒（MHV-A59）感染的影响。

感染了小鼠肝炎A59病毒（MHV-A59）的小鼠对肝肾富马酰乙酰乙酸水解酶（FAH）产生肝炎和自身抗体（autoAb），这一事实与警报蛋白如尿酸和/或高迁移率小组的释放密切相关蛋白1（HMGB1）。我们在小鼠MHV-A59感染模型中研究了针对IL-17A的中和单克隆抗体（MAb）的作用。MAb抗IL-17F和抗IFNγ用于补充研究。结果表明，用MAb抗IL-17A抗体治疗的MHV-A59感染小鼠的转氨酶水平明显降低，而血浆Ig浓度则急剧升高。相反，MAb抗IL-17F可增强转氨酶的释放，并且不影响Ig水平。在感染了MHV-A59的小鼠中检测到血清IFNγ，并且在MAb抗IL-17A给药后其浓度升高。除了，MAb抗IFNγ大大提高了转氨酶的血浆水平。IL-17A中和不影响MHV-A59诱导的HMGB1释放和血浆尿酸浓度略有增加。但是，用MAb治疗的小鼠无法产生FAH的autoAb。以上结果表明，对不同的MHV-A59效应起作用的Th1和Th17细胞具有相互调节作用。另外，提出IL-17A参与警报蛋白的佐剂作用，导致autoAb表达。