哮喘联盟

    背景：哮喘是一系列复杂的炎症反应，它分为轻度、中度和重度持续性哮喘。成功的治疗依赖于对不同严重程度哮喘炎症反应作用机制的理解。本研究的目的是分析在轻度间歇哮喘和重度持续哮喘患者病情加重过程中，在细胞凋亡，CD4/CD8比值，记忆细胞间隔，外周血淋巴细胞Th1和Th2细胞特征上的差异。
    结果：应用外周血淋巴细胞免疫细胞化学染色研究了轻度哮喘、重度哮喘、健康人群在上述四方面的差异。抗凋亡和凋亡前体蛋白以Bcl-2/Bax比值进行衡量，CD4+/CD8+比值作为CD8的标志，记忆细胞与幼稚细胞的比值(CD45RO+/CD45RA+)作为CD45RO+及CD45RA+的标志，通过酶联免疫吸附试验(ELISA)测定IL-4/IFN-γ比值代表Th2/Th1细胞因子的平衡，从而确定体外淋巴细胞细胞因子的合成状态。结果发现，重度哮喘组Bcl-2/Bax比值较轻度哮喘组高，并且轻度哮喘组又高于健康对照组。重度哮喘组中记忆/幼稚淋巴细胞比值高于轻度哮喘组。此外，重度和轻度哮喘患者组的记忆细胞，CD45RO+和CD45RO + /CD45RA +比值与Bcl-2/Bax呈正相关。与此相反，健康对照组，轻度和严重哮喘组的CD4 +/CD8 +比值无显著差异。然而，仅在重度哮喘患者中，CD8 +细胞与记忆细胞，CD45RO有直接相关。有趣的是，细胞因子最明显的变化是轻度哮喘患者以Th2细胞表达为主、重度哮喘患者以Th1细胞表达为主，而重度哮喘患者的体外IL-4/IFN-γ比例最低，γ-干扰素表达最高。
    结论：不同严重程度的哮喘的炎症发生机制有很大差别。轻度间歇性哮喘加重过程中主要是Th2细胞变应原介导的反应，有良好的细胞凋亡水平使炎症具有自限性，而重度持续性哮喘的炎症反应主要是由Th1细胞介导，细胞凋亡逐步减少、记忆细胞增多，CD45RO +增高，最终导致炎症持续发生。

（林江涛 审校）
Abdulamir AS, et al. BMC Immunol. 2008 Dec 16;9(1):73. [Epub ahead of print]

Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma.

Abdulamir AS, Hafidh RR, Abubakar F, Abbas KA.

ABSTRACT:
BACKGROUND: Asthma is a complicated network of inflammatory reactions. It is classified into mild, moderate, and severe persistent asthma. The success of asthma therapy relies much on understanding the underlying mechanisms of inflammation at each stage of asthma severity. The aim of this study was to explore the differences in apoptotic potential, CD4/CD8 ratio, memory compartment, and T- helper (Th) 1 and 2 profile of peripheral blood lymphocytes (PBL) in patients with mild intermittent asthma and severe persistent asthma during exacerbation periods.
RESULTS: Four research lines were investigated and compared among mild asthmatics, severe asthmatics, and healthy groups by applying immunocytochemical staining of PBL. Antiapoptotic and proapoptotic proteins with Bcl-2/Bax ratio, CD4, CD8 markers with CD4+/CD8+ ratio, CD45RO+, CD45RA+ markers with memory/naive ratio (CD45RO+/CD45RA+). Th2/Th1 cytokines balance represented by IL-4/IFN-gamma ratio was measured by enzyme-linked immunosorbent assay (ELISA) for in vitro PBL cytokine synthesis. It was found that Bcl-2/Bax ratio was higher in severe than in mild asthmatics which in turn was higher than in healthy group. And memory/naive ratio of PBL was higher in severe than in mild asthmatics. Moreover, memory cells, CD45RO+ and CD45RO+/CD45RA+ ratio were correlated directly with Bcl-2/Bax, in severe and mild asthma patients. In contrast, CD4+/CD8+ ratio was not changed significantly among healthy group, mild and severe asthmatics. However, CD8+ cells were correlated directly with memory cells, CD45RO+, in severe asthmatics only. Interestingly, the dominant profile of cytokines appeared to change from T helper 2 (Th2) in mild asthmatics to T helper 1 (Th1) in severe asthmatics where the lowest in vitro IL-4/IFN-gamma ratio and highest IFN-gamma were found.

CONCLUSIONS: It was concluded that the underlying mechanisms of inflammation might vary greatly with asthma stage of severity. Mild intermittent asthma is mainly Th2 allergen-oriented reaction during exacerbations with good level of apoptosis making the inflammation as self-limiting, while in severe persistent asthma, the inflammatory reaction mediated mainly by Th1 cytokines with progressive loss of apoptosis leading to longer exacerbations, largely expanded memory cells, CD45RO+, leading to persistent baseline inflammation.