Kasaian Marion T, Miller Douglas K
Department of Discovery Inflammation, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA.
Biochem Pharmacol. 2008 Jul 15;76(2):147-55. doi: 10.1016/j.bcp.2008.04.002. Epub 2008 Apr 16.
Interleukin-13 (IL-13) is a critical mediator of asthma pathology. On B cells, monocytes, epithelial cells, and smooth muscle cells, IL-13 acts through the IL-13Ralpha1/IL-4Ralpha complex to directly induce activation responses that contribute to atopic disease. In human populations, genetic polymorphisms in IL-13, its receptor components, or the essential signaling element STAT6, have all been associated with increased risk of atopy and asthma. Animal studies using IL-13 deficient mice, IL-13 transgenic animals, and IL-13 neutralization strategies have confirmed an essential role for this cytokine in driving major correlates of asthma pathology, including airway hyperresponsiveness (AHR), lung eosinophilia, mucus generation, and fibrosis. Ongoing studies continue to define both overlapping and distinct roles for IL-13 and the related cytokine, IL-4, in promoting asthmatic changes. Furthermore, new evidence concerning the role of the "decoy" receptor, IL-13Ralpha2, has prompted re-evaluation of the receptor forms that underlie the numerous activities of IL-13. In this review, we summarize the essential role of IL-13 in asthma, compare the relative contributions of IL-13 and IL-4 to key aspects of the asthmatic phenotype, and outline novel therapeutic strategies to target this critical cytokine.
白细胞介素-13（IL-13）是哮喘病理过程中的关键介质。在B细胞、单核细胞、上皮细胞和平滑肌细胞上，IL-13通过IL-13Rα1/IL-4Rα复合物发挥作用，直接诱导激活反应，这些反应会导致特应性疾病。在人类群体中，IL-13、其受体成分或关键信号元件信号转导和转录激活因子6（STAT6）的基因多态性均与特应性和哮喘风险增加有关。使用IL-13缺陷小鼠、IL-13转基因动物以及IL-13中和策略的动物研究证实了这种细胞因子在引发哮喘病理主要相关因素（包括气道高反应性（AHR）、肺部嗜酸性粒细胞增多、黏液生成和纤维化）中起重要作用。正在进行的研究继续明确IL-13和相关细胞因子IL-4在促进哮喘变化中的重叠和不同作用。此外，关于“诱饵”受体IL-13Rα2作用的新证据促使人们重新评估构成IL-13多种活性基础的受体形式。在本综述中，我们总结了IL-13在哮喘中的重要作用，比较了IL-13和IL-4对哮喘表型关键方面的相对贡献，并概述了针对这种关键细胞因子的新型治疗策略。
