1 MedImmune Ltd, Cambridge, United Kingdom.
Am J Respir Cell Mol Biol. 2014 May;50(5):985-94. doi: 10.1165/rcmb.2013-0342OC.
The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung.
肺中的异常纤维化和修复反应是特发性肺纤维化（IPF）的主要特征。临床上已经使用了许多抗纤维化策略，但收效甚微，这表明在这种疾病中，有效的治疗策略必须抑制纤维化并促进适当的肺修复机制。IL-13 是 IPF 中的一个有吸引力的靶点，但它的疾病相关性和作用机制尚不清楚。在本研究中，IL-13 的过度表达及其途径标志物与 IPF 相关，特别是与这种疾病的快速进展形式相关。使用 tralokinumab（CAT354）在人源化的肺纤维化实验模型中靶向 IL-13 被发现可在该模型中治疗性阻断异常的肺重塑。然而，靶向 IL-13 也被发现可促进肺修复并恢复上皮完整性。因此，靶向 IL-13 可抑制肺纤维化过程并增强肺修复过程。
