阿奇霉素抑制哮喘患儿Th2细胞产生IL-5
2011/07/06
摘要
背景：儿童哮喘是一种Th2细胞驱动的炎症性气道疾病，表现为反复发作的气道梗阻。阿奇霉素（AZM）为大环内酯类抗生素，除了抗菌作用外，还具有抗炎活性。因此，可能有助于哮喘患儿的治疗。本研究旨在检测AZM对哮喘患儿和非特应性对照者Th2细胞的影响。
方法：从9名哮喘患者和9名非特应性患者外周血分离CD4+细胞。诱导细胞活化为Th0细胞，并分化为Th2细胞。通过检测细胞增殖和细胞因子产生，研究AZM对活化的CD4+细胞的影响。
结果：与非特应性对照相比，哮喘患儿来源的Th0和Th2 CD4+ T细胞能产生更多的IL-5（Th2细胞因子），但产生的IFN-γ（Th1细胞因子）较低。AZM能以一种剂量依赖性方式，抑制过敏性哮喘患者Th0和Th2细胞IL-5的产生，但不影响IL-13和IFN-γ的产生。在非特应性对照来源的细胞也具有类似结果，除了AZM能抑制Th0细胞的IFN-γ产生。AZM在高剂量时，通过抑制CD4+ T细胞增殖和增加细胞凋亡，降低细胞活性，该作用对Th0和Th2的影响类似。但是哮喘患儿和对照间无显著差异。
结论：研究结果显示，AZM能显著降低哮喘患儿Th2细胞的IL-5产生，表明AZM对于哮喘控制的患儿具有治疗作用。
（苏楠 审校）
Int Arch Allergy Immunol. 2011 May 18;156(2):179-186. [Epub ahead of print]
Azithromycin Inhibits IL-5 Production of T Helper Type 2 Cells from Asthmatic Children.
Lin SJ, Lee WJ, Liang YW, Yan DC, Cheng PJ, Kuo ML.
Source
Division of Asthma, Allergy, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
Abstract
BACKGROUND: Childhood asthma is a type 2 helper T (Th2) cell-driven inflammatory airway disease characterized by recurrent episodes of airway obstruction. Azithromycin (AZM), a macrolide antibiotic exhibiting anti-inflammatory activity aside from its antibacterial effect, may prove beneficial for asthmatic children. This study aimed to determine the effect of AZM on Th2 cells from atopic asthmatic children and non-atopic controls.
METHODS: CD4+ cells were isolated from peripheral blood mononuclear cells of 9 patients with asthma and 9 non-atopic individuals. Cells were activated as Th0 and differentiated into Th2 cells. The effect of AZM on activated CD4+ cells was evaluated with respective cell proliferation and cytokine production.
RESULTS: Th0 and Th2 CD4+ T cells from atopic asthmatic children produced greater interleukin (IL)-5 (Th2 cytokine) but lower interferon (IFN)-γ (Th1 cytokine) compared to the non-atopic controls, respectively. AZM inhibited IL-5 production of Th0 and Th2 cells from atopic asthmatics in a dose-dependent fashion, without significantly affecting their IL-13 and IFN-γ production. A similar effect was observed in non-atopic controls except that AZM did inhibit IFN-γ production of their Th0 cells. AZM at a higher dose decreased cell viability by inhibiting CD4+ T cell proliferation and enhanced their apoptosis, an effect similarly observed in Th0 and Th2 cells, and did not differ between asthmatic children and controls.
CONCLUSION: Our finding that AZM preferentially downregulates IL-5 production suggests its therapeutic potentials in controlling childhood asthma.
Int Arch Allergy Immunol. 2011 May 18;156(2):179-186. [Epub ahead of print]
