Inman Robert D, Chiu Basil
Toronto Western Research Institute, University of Toronto, Toronto, Ontario, Canada.
Arthritis Rheum. 2006 Feb;54(2):499-507. doi: 10.1002/art.21643.
Although Chlamydia trachomatis-induced arthritis is among the most common rheumatic diseases having an identified infectious trigger, the pathogenesis of this arthritis is not well defined. We sought to investigate the host-microbe interactions that contribute to the severity of arthritis initiated by chlamydial infection.
We established an experimental rat model of C. trachomatis-induced arthritis that recapitulates many pathologic features of the clinical disease. The severity of the arthritis was defined using an established histopathologic scoring system. Host clearance of the pathogen and local cytokine production were examined by enzyme-linked immunosorbent assays.
Lewis rats were susceptible to C. trachomatis-induced arthritis, whereas BN rats were relatively resistant to this disease. Significant differences in the histopathologic severity of arthritis were originally observed on day 21, and this prompted an examination of the acute phase of the arthritis. As early as day 5 after the onset of the arthritis, pathologic changes in Lewis rats were more severe than those in BN rats. An evaluation of the role of complement using cobra venom factor treatment excluded complement as being the key to differential sensitivity, because decomplementation did not eliminate the differences in arthritis severity between Lewis and BN rats. Host clearance, in contrast, was significantly different between the rat strains, with BN rats showing more prompt and effective clearance of the pathogen from both synovial tissues and spleen compared with Lewis rats. Local cytokine profiles demonstrated that host resistance was characterized by enhanced synovial expression of tumor necrosis factor alpha, interferon-gamma (IFNgamma), and interleukin-4.
These studies demonstrated that cytokines thought to be proinflammatory in nature can play an important role in host defense in infection-triggered arthritis and serve to highlight the dynamic cytokine relationships that constitute effective host-pathogen interactions.
虽然沙眼衣原体诱导的关节炎是最常见的具有明确感染诱因的风湿性疾病之一，但这种关节炎的发病机制尚未完全明确。我们试图研究导致衣原体感染引发关节炎严重程度的宿主-微生物相互作用。
我们建立了一个沙眼衣原体诱导的关节炎实验大鼠模型，该模型概括了临床疾病的许多病理特征。使用既定的组织病理学评分系统来定义关节炎的严重程度。通过酶联免疫吸附测定法检测病原体的宿主清除情况和局部细胞因子的产生。
Lewis大鼠易患沙眼衣原体诱导的关节炎，而BN大鼠对这种疾病相对具有抗性。最初在第21天观察到关节炎组织病理学严重程度存在显著差异，这促使我们对关节炎急性期进行检查。早在关节炎发作后的第5天，Lewis大鼠的病理变化就比BN大鼠更严重。使用眼镜蛇毒因子治疗评估补体的作用，排除了补体是差异敏感性的关键因素，因为去补体并没有消除Lewis大鼠和BN大鼠之间关节炎严重程度的差异。相比之下，不同品系大鼠的宿主清除情况存在显著差异，与Lewis大鼠相比，BN大鼠能更迅速有效地从滑膜组织和脾脏中清除病原体。局部细胞因子谱显示，宿主抵抗力的特征是滑膜中肿瘤坏死因子α、干扰素-γ（IFNγ）和白细胞介素-4的表达增强。
这些研究表明，被认为具有促炎性质的细胞因子在感染引发的关节炎的宿主防御中可发挥重要作用，并有助于突出构成有效宿主-病原体相互作用的动态细胞因子关系。
