Wauwe J V
Department of Immunology, Janssen Research Foundation, Beerse, Belgium.
Drug News Perspect. 2000 May;13(4):197-205.
Increased accumulation of eosinophils in bronchial mucosa is a hallmark of bronchial asthma. Upon activation, these eosinophils synthesize and release an array of proinflammatory and cytotoxic products that cause edema, mucus secretion, tissue damage and airway hyperreactivity. Maturation, activation and survival of eosinophils are largely dependent on the availability of the hematopoietic cytokine interleukin-5 (IL-5), produced by activated T-helper type 2 (Th2) lymphocytes. Numerous findings obtained in animal models of asthma, utilizing IL-5 transgenic mice or anti-IL-5 antibodies, have underscored the key contribution of this cytokine to the allergic process. Clinical studies in humans have also indicated the close correlation between airway IL-5 expression, eosinophilia and asthma symptoms. Taken together, these findings have advanced IL-5 to a potentially successful target for asthma treatment. Current tactics to tackle IL-5 are neutralization of IL-5, IL-5 receptor antagonism, interference with IL-5-induced intracellular signaling and inhibition of IL-5 biosynthesis.
支气管黏膜中嗜酸性粒细胞的积聚增加是支气管哮喘的一个标志。激活后，这些嗜酸性粒细胞合成并释放一系列促炎和细胞毒性产物，导致水肿、黏液分泌、组织损伤和气道高反应性。嗜酸性粒细胞的成熟、激活和存活很大程度上依赖于活化的2型辅助性T（Th2）淋巴细胞产生的造血细胞因子白细胞介素-5（IL-5）。利用IL-5转基因小鼠或抗IL-5抗体在哮喘动物模型中获得的大量研究结果强调了这种细胞因子对过敏过程的关键作用。在人类中的临床研究也表明气道IL-5表达、嗜酸性粒细胞增多与哮喘症状之间密切相关。综上所述，这些研究结果使IL-5成为哮喘治疗一个潜在的成功靶点。目前针对IL-5的策略包括中和IL-5、拮抗IL-5受体、干扰IL-5诱导的细胞内信号传导以及抑制IL-5生物合成。
