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多中心性淋巴瘤犬与健康犬血清细胞因子水平的比较。

Comparison of serum cytokine levels between dogs with multicentric lymphoma and healthy dogs.

作者信息

Calvalido Jerome, Wood Geoffrey A, Mutsaers Anthony J, Wood Darren, Sears William, Woods J Paul

机构信息

Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

出版信息

Vet Immunol Immunopathol. 2016 Dec;182:106-114. doi: 10.1016/j.vetimm.2016.10.009. Epub 2016 Oct 19.

Abstract

In humans, multiple cytokines have been linked to the development of lymphoma, and are relevant biomarkers for response to chemotherapy and prognosis. In contrast, only a few circulating cytokines have been studied in dogs with lymphoma. We prospectively enrolled thirty-one dogs newly diagnosed with multicentric lymphoma. Immunophenotype was determined by flow cytometry in all dogs, separating them into 2 subgroups: B cell lymphoma (n=21) and T cell lymphoma (n=10). Nineteen healthy dogs were enrolled in the control group. Circulating cytokine concentrations were measured using a commercial canine multiplex magnetic bead-based assay which included Interleukin-2 (IL-2), IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), Tumor Necrosis Factor-α (TNF-α), Interferon γ (IFN-γ), IFN-γ induced Protein-10 (IP-10), Keratinocyte Chemoattractant-like (KC-like), and Monocyte Chemoattractant Protein-1 (MCP-1). The serum levels of each cytokine were first compared between the lymphoma and control groups, and then between the B cell lymphoma, T cell lymphoma, and control groups. There was no significant difference between the lymphoma and healthy control groups regarding sex, age and weight. MCP-1, IL-6, and IL-10 were significantly higher in dogs with lymphoma compared to healthy dogs (p<0.01, p=0.01 and p=0.03, respectively). MCP-1 and IL-10 were significantly higher in the B cell lymphoma group than in the healthy group (p=0.01, p=0.01, respectively). MCP-1 and IL-6 levels were significantly higher in the T cell lymphoma group than in the healthy group (p=0.02, p<0.01, respectively). IL-6 was significantly higher in the T cell lymphoma group than in the B cell lymphoma group (p=0.03). Significant differences among the groups were found for IL-15 and KC-like, but they were affected by age and/or sex. There were no significant differences in serum IL-2, IL-7, IL-8, IL-18, GM-CSF, TNF-α, IFN-γ, and IP-10 between any of the groups. Significant differences in red blood cell, white blood cell, neutrophil, lymphocyte and monocyte counts were also found between the different groups of dogs. Our data showed different serum cytokine and peripheral blood cell profiles between dogs with lymphoma and healthy dogs, and between dogs with B cell and T cell lymphoma. Further study is necessary to investigate the role of these cytokines in lymphoma pathogenesis, response to treatment, and prognosis, and the influence of age, sex and blood cell counts on their expression.

摘要

在人类中,多种细胞因子与淋巴瘤的发生发展有关,并且是化疗反应和预后的相关生物标志物。相比之下,在患淋巴瘤的犬类中,仅对少数循环细胞因子进行了研究。我们前瞻性地纳入了31只新诊断为多中心淋巴瘤的犬。通过流式细胞术确定所有犬的免疫表型,将它们分为2个亚组:B细胞淋巴瘤(n = 21)和T细胞淋巴瘤(n = 10)。19只健康犬被纳入对照组。使用基于商业犬类多重磁珠的检测方法测量循环细胞因子浓度,该检测方法包括白细胞介素-2(IL-2)、IL-6、IL-7、IL-8、IL-10、IL-15、IL-18、粒细胞巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子-α(TNF-α)、干扰素γ(IFN-γ)、IFN-γ诱导蛋白-10(IP-10)、角质形成细胞趋化因子样(KC样)和单核细胞趋化蛋白-1(MCP-1)。首先比较淋巴瘤组和对照组之间每种细胞因子的血清水平,然后比较B细胞淋巴瘤组、T细胞淋巴瘤组和对照组之间的血清水平。淋巴瘤组和健康对照组在性别、年龄和体重方面无显著差异。与健康犬相比,患淋巴瘤的犬的MCP-1、IL-6和IL-10显著更高(分别为p<0.01、p = 0.01和p = 0.03)。B细胞淋巴瘤组的MCP-1和IL-10显著高于健康组(分别为p = 0.01、p = 0.01)。T细胞淋巴瘤组的MCP-1和IL-6水平显著高于健康组(分别为p = 0.02、p<0.01)。T细胞淋巴瘤组的IL-6显著高于B细胞淋巴瘤组(p = 0.03)。在IL-15和KC样方面发现组间存在显著差异,但它们受年龄和/或性别的影响。任何组之间的血清IL-2、IL-7、IL-8、IL-18、GM-CSF、TNF-α、IFN-γ和IP-10均无显著差异。在不同组的犬之间还发现红细胞、白细胞、中性粒细胞、淋巴细胞和单核细胞计数存在显著差异。我们的数据显示,患淋巴瘤的犬与健康犬之间,以及B细胞淋巴瘤犬和T细胞淋巴瘤犬之间,血清细胞因子和外周血细胞谱不同。有必要进一步研究这些细胞因子在淋巴瘤发病机制、治疗反应和预后中的作用,以及年龄、性别和血细胞计数对其表达的影响。

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