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[早期和晚期莱姆病患者血清中的转化生长因子β、金属蛋白酶2及其组织抑制剂2]

[Transforming growth factor beta, metalloproteinase 2 and its tissue inhibitor 2 in the serum from patients with early and late boreliosis].

作者信息

Pancewicz Sławomir A, Izycka Aneta, Klibingat Marcin, Zajkowska Joanna M, Swierzbińska-Pijanowska Renata, Kondrusik Maciej, Grygorczuk Sambor S, Izycki Tomasz, Hermanowska-Szpakowicz Teresa

机构信息

Uniwersytet Medyczny w Białymstoku, Klinika Chorób Zakaźnych i Neuroinfekcji.

出版信息

Pol Merkur Lekarski. 2008 Dec;25(150):495-9.

Abstract

UNLABELLED

Boreliosis is an arthropod transmitted, bacterial infection, known for its complicated pathogenesis and prolonged course. Boreliosis can be divided into early, localized type, early generalized type as well as late type. Cytokines control homeostasis of the organism by transmitting signals between cells. TGF (transforming growth factor) beta is one of the cytokines that modulates cell differentiation, proliferation and angiogenesis. In larger concentrations it blocks the expression of IL-1 and TNF-alfa. TGF-beta stimulates production of selectin, collagen, fibrinoectin and integrin. It inhibits metalloproteinase that causes degradation of the above mentioned proteins.

THE AIM OF THE STUDY

We assessed a concentration of TGF-beta in the blood of patients presented with an early form of boreliosis Erythema Migrans (EM) as well as in patients with an advanced form of this disease Lyme arthritis (LA) In addition, levels of metalloproteinase (MMP-2), its tissue inhibitor (TIMP) was assessed. We attempted to analyze the effects of treatment by measuring specific markers of inflammation.

MATERIAL AND METHODS

We tested a group of 40 patients with Lyme disease. The first group included 20 patients with an early form--(EM), while the second group of 20 patients, had a chronic form of the disease--(LA). The control group consisted of 8 healthy blood donors. The serum levels of TGF beta, metalloproteinase (MMP-2) and its tissue inhibitor (TIMP-2) were obtained using ELISA. Levels were obtained prior to treatment and after 4 weeks of treatment with Doxycyclin or Rocephin (Ceftriaxon).

RESULTS

The results indicated that levels of TGF-beta were lower in the Lyme patients than in the healthy control. In the patients group, the early form of disease had higher levels of TGF-beta than in the chronic. Acute, early phase group had also higher serum levels of MMP-2 and TIMP-2 in comparison to the chronic stage group. LA group showed correlation between TGF-beta concentration and levels of MMP-2. It has not been the case in the acute stage of the disease. Both groups of patients had higher levels of IL-1-aRII and selectin E in comparison with control.

CONCLUSIONS

As suggested by the results, decreased levels of TGF-beta in patients with boreliosis can be due to increased levels of MMP-2 and TIMP. The above markers and their concentration can be useful in the monitoring of the effectiveness of provided therapy and suggest that inflammation can persist in spite of the normalization of the clinical picture. The results suggest extremely complicated pathophysiology of Lyme disease where pro and antiinflammatory cytokines are as important as the pathogen itself.

摘要

未标注

莱姆病是一种由节肢动物传播的细菌感染疾病,以其复杂的发病机制和病程迁延而闻名。莱姆病可分为早期局限性、早期播散性以及晚期。细胞因子通过在细胞间传递信号来控制机体的内环境稳定。转化生长因子(TGF)β是调节细胞分化、增殖和血管生成的细胞因子之一。在较高浓度时,它会阻断白细胞介素-1(IL-1)和肿瘤坏死因子-α(TNF-α)的表达。TGF-β刺激选择素、胶原蛋白、纤连蛋白和整合素的产生。它抑制导致上述蛋白质降解的金属蛋白酶。

研究目的

我们评估了患有早期莱姆病游走性红斑(EM)患者以及患有该疾病晚期莱姆关节炎(LA)患者血液中TGF-β的浓度。此外,还评估了金属蛋白酶(MMP-2)及其组织抑制剂(TIMP)的水平。我们试图通过测量炎症的特定标志物来分析治疗效果。

材料与方法

我们测试了一组40例莱姆病患者。第一组包括20例早期患者(EM),而第二组20例患者患有该疾病的慢性形式(LA)。对照组由8名健康献血者组成。使用酶联免疫吸附测定法(ELISA)获得TGF-β、金属蛋白酶(MMP-2)及其组织抑制剂(TIMP-2)的血清水平。在使用强力霉素或头孢曲松(头孢三嗪)治疗前及治疗4周后获取这些水平。

结果

结果表明,莱姆病患者的TGF-β水平低于健康对照组。在患者组中,疾病的早期形式比慢性形式具有更高的TGF-β水平。与慢性期组相比,急性期早期组的血清MMP-2和TIMP-2水平也更高。LA组显示TGF-β浓度与MMP-2水平之间存在相关性。在疾病的急性期并非如此。与对照组相比,两组患者的IL-1-aRII和选择素E水平均较高。

结论

结果表明,莱姆病患者TGF-β水平降低可能是由于MMP-2和TIMP水平升高所致。上述标志物及其浓度可用于监测所提供治疗的有效性,并表明尽管临床表现恢复正常,但炎症可能仍然存在。结果表明莱姆病的病理生理学极其复杂,其中促炎和抗炎细胞因子与病原体本身同样重要。

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