在抗生素难治性莱姆关节炎病程中，关节液和滑膜组织中存在高水平的炎性趋化因子和细胞因子。

High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory lyme arthritis.

作者信息

Shin Junghee J, Glickstein Lisa J, Steere Allen C

机构信息

Massachusetts General Hospital, and Harvard Medical School, Boston, Massachussets 02114, USA.

出版信息

Arthritis Rheum. 2007 Apr;56(4):1325-35. doi: 10.1002/art.22441.

DOI:10.1002/art.22441

PMID:17393419

Abstract

OBJECTIVE

To investigate the possible role of chemokines and cytokines in the pathogenesis of Lyme arthritis.

METHODS

Using cytometric bead array and flow cytometry techniques, chemokine and cytokine levels were determined in 65 synovial fluid (SF) samples and 7 synovial tissue (ST) samples from 17 patients with antibiotic-responsive Lyme arthritis and 35 patients with antibiotic-refractory Lyme arthritis seen during the past 18 years. In the ST samples, expression of chemokine receptors was measured using immunohistochemistry.

RESULTS

Before or during antibiotic therapy, when the majority of patients had positive polymerase chain reaction (PCR) results for Borrelia burgdorferi DNA, SF from patients with antibiotic-refractory arthritis contained exceptionally high levels of Th1 chemoattractants and cytokines, particularly CXCL9 and interferon-gamma (IFNgamma). Compared with the patients whose arthritis was responsive to antibiotic treatment, those with antibiotic-refractory arthritis had significantly higher levels of CXCL9 and CXCL10 (both P<or=0.001) and CCL3, CCL4, CXCL8, IFNgamma, tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-6 (all P<or=0.01). During the post-antibiotic period, when the results of PCR for B burgdorferi DNA in SF and ST were uniformly negative, patients with antibiotic-refractory arthritis continued to exhibit high SF and ST levels of these chemokines and cytokines. In addition, synovial samples showed marked expression of the receptors for T cell or macrophage chemokines, CXCR3 and CCR5.

CONCLUSION

Patients with antibiotic-refractory Lyme arthritis have high synovial fluid levels of proinflammatory chemokines and cytokines, especially CXCL9 and IFNgamma, throughout the illness. Thus, even when antibiotic treatment reduces or completely clears the infection in these patients, the inflammatory response in synovium persists.

摘要

目的

探讨趋化因子和细胞因子在莱姆关节炎发病机制中的可能作用。

方法

采用细胞计数珠阵列和流式细胞术，对过去18年中收治的17例抗生素反应性莱姆关节炎患者和35例抗生素难治性莱姆关节炎患者的65份滑液（SF）样本和7份滑膜组织（ST）样本中的趋化因子和细胞因子水平进行了测定。在ST样本中，采用免疫组织化学法检测趋化因子受体的表达。

结果

在抗生素治疗前或治疗期间，大多数患者的伯氏疏螺旋体DNA聚合酶链反应（PCR）结果呈阳性，抗生素难治性关节炎患者的SF中Th1趋化因子和细胞因子水平异常高，尤其是CXCL9和干扰素-γ（IFNγ）。与关节炎对抗生素治疗有反应的患者相比，抗生素难治性关节炎患者的CXCL9和CXCL10水平显著更高（均P≤0.001），CCL3、CCL4、CXCL8、IFNγ、肿瘤坏死因子α、白细胞介素-1β（IL-1β）和IL-6水平也显著更高（均P≤0.01）。在抗生素治疗后时期，当SF和ST中伯氏疏螺旋体DNA的PCR结果均为阴性时，抗生素难治性关节炎患者的SF和ST中这些趋化因子和细胞因子水平仍持续较高。此外，滑膜样本显示T细胞或巨噬细胞趋化因子CXCR3和CCR5的受体有明显表达。