BACKGROUND The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice. METHODS Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated. RESULTS Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice. CONCLUSION These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.

中文翻译：

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IL35 调节改变了小鼠疟疾感染期间的存活率、细胞因子环境和组织病理学后果。

背景技术 IL-35 在多种人类疾病中的免疫调节潜力已有报道。在认识到炎症细胞因子激活及其在疟疾感染期间介导病理学的优势后，该研究旨在表征伯氏疟原虫（ANKA 株）感染小鼠中 IL-35 的表达和功能贡献。方法 使用雄性 ICR 小鼠的伯氏疟原虫感染作为啮齿动物模型。分别通过酶联免疫吸附测定和免疫组织化学评估伯氏疟原虫感染小鼠及其健康对照小鼠的体循环和组织中IL-35表达的时间过程。通过流式细胞术评估重组IL-35蛋白调节IL-35或中和抗Epstein-Barr病毒诱导的基因3抗体对伯氏疟原虫感染期间细胞因子环境的影响。此外，还评估了调节 IL-35 对疟疾组织病理学特征和疾病进展的影响。结果白细胞介素35在伯氏疟原虫感染小鼠的血清和组织中显着上调，并且与寄生虫血症相关。IL-35 的中和显着增强了 IFN-γ 的释放，降低了 IL-6 的表达并降低了寄生虫血症的通畅性。IL-35 的中和还与生存率增加的趋势以及不存在与疟疾感染相关的病理特征相关，这与重组 IL-35 蛋白的施用不同，重组 IL-35 蛋白的施用维持了伯氏疟原虫的正常感染过程和不利的疟疾相关组织学结果被感染的老鼠。结论 这些结果表明 IL-35 参与伯氏疟原虫诱导的疟疾感染。IL-35 中和策略可能代表有利于解决疟疾感染的可行治疗方式。