Excessive Pro-Inflammatory Serum Cytokine Concentrations in Virulent Canine Babesiosis

Babesia rossi infection causes a severe inflammatory response in the dog, which is the result of the balance between pro- and anti-inflammatory cytokine secretion. The aim of this study was to determine whether changes in cytokine concentrations were present in dogs with babesiosis and whether it was associated with disease outcome. Ninety-seven dogs naturally infected with B. rossi were studied and fifteen healthy dogs were included as controls. Diagnosis of babesiosis was confirmed by polymerase chain reaction and reverse line blot. Blood samples were collected from the jugular vein at admission, prior to any treatment. Cytokine concentrations were assessed using a canine-specific multiplex assay on an automated analyser. Serum concentrations of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-18, granulocyte-macrophage colony stimulating factor (GM-CSF) and monocyte chemotactic protein-1 (MCP-1) were measured. Twelve of the Babesia-infected dogs died (12%) and 85 survived (88%). Babesia-infected dogs were also divided into those that presented within 48 hours from displaying clinical signs, and those that presented more than 48 hours after displaying clinical signs. Cytokine concentrations were compared between the different groups using the Mann-Whitney U test. IL-10 and MCP-1 concentrations were significantly elevated for the Babesia-infected dogs compared to the healthy controls. In contrast, the IL-8 concentration was significantly decreased in the Babesia-infected dogs compared to the controls. Concentrations of IL-6 and MCP-1 were significantly increased in the non-survivors compared to the survivors. Concentrations for IL-2, IL-6, IL-18 and GM-CSF were significantly higher in those cases that presented during the more acute stage of the disease. These findings suggest that a mixed cytokine response is present in dogs with babesiosis caused by B. rossi, and that an excessive pro-inflammatory response may result in a poor outcome.罗氏巴贝斯虫（Babesia rossi）感染可引发犬类严重炎症反应，该反应的发生取决于促炎与抗炎细胞因子的分泌平衡。本研究旨在探究巴贝斯虫病（babesiosis）患犬的细胞因子浓度是否存在变化，以及该变化是否与疾病转归相关。本研究纳入97只自然感染罗氏巴贝斯虫的患犬，另以15只健康犬作为对照。巴贝斯虫病的确诊通过聚合酶链式反应（polymerase chain reaction, PCR）与反向线点杂交（reverse line blot）完成。所有受试犬在入院后、接受任何治疗前，均经颈静脉采集血液样本。采用犬源特异性多重检测技术，在自动化分析仪上检测细胞因子浓度。本次检测了血清中白细胞介素（interleukin, IL）-2、IL-6、IL-8、IL-10、IL-18、粒细胞-巨噬细胞集落刺激因子（granulocyte-macrophage colony stimulating factor, GM-CSF）以及单核细胞趋化蛋白-1（monocyte chemotactic protein-1, MCP-1）的浓度。感染罗氏巴贝斯虫的犬只中，12只（12%）死亡，85只（88%）存活。研究同时将感染犬只按出现临床症状后的就诊时间分为两组：出现症状48小时内就诊者，以及出现症状超过48小时后就诊者。采用曼-惠特尼U检验（Mann-Whitney U test）对不同组间的细胞因子浓度进行比较。与健康对照组相比，感染犬只的IL-10与MCP-1浓度显著升高。与之相反，感染犬只的IL-8浓度较对照组显著降低。非存活组犬只的IL-6与MCP-1浓度显著高于存活组。在疾病急性期就诊的病例中，IL-2、IL-6、IL-18与GM-CSF的浓度显著更高。上述结果表明，罗氏巴贝斯虫感染引发的巴贝斯虫病患犬体内存在混合细胞因子应答，且过度的促炎反应可能导致不良疾病转归。