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Interleukin-11 Is a Therapeutic Target in Idiopathic Pulmonary Fibrosis

Interleukin-11 Is a Therapeutic Target in Idiopathic Pulmonary Fibrosis

Benjamin Ng, Jinrui Dong, Giuseppe D'Agostino, Sivakumar Viswanathan, Anissa A Widjaja, Wei-Wen Lim, Nicole S J Ko, Jessie Tan, Sonia P Chothani, Benjamin Huang, Chen Xie, Chee Jian Pua, Ann-Marie Chacko, etc.

Sci Transl Med. 2019 Sep 25;11(511):eaaw1237.

PMID: 31554736

Abstract:

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease where invasive pulmonary myofibroblasts secrete collagen and destroy lung integrity. Here, we show that interleukin-11 (IL11) is up-regulated in the lung of patients with IPF, associated with disease severity, and IL-11 is secreted from IPF fibroblasts. In vitro, IL-11 stimulates lung fibroblasts to become invasive actin alpha 2, smooth muscle-positive (ACTA2+), collagen-secreting myofibroblasts in an extracellular signal-regulated kinase (ERK)-dependent, posttranscriptional manner. In mice, fibroblast-specific transgenic expression or administration of murine IL-11 induces lung myofibroblasts and causes lung fibrosis. IL-11 receptor subunit alpha-1 (Il11ra1)-deleted mice, whose lung fibroblasts are unresponsive to profibrotic stimulation, are protected from fibrosis in the bleomycin mouse model of pulmonary fibrosis. We generated an IL-11-neutralizing antibody that blocks lung fibroblast activation downstream of multiple stimuli and reverses myofibroblast activation. In therapeutic studies, anti-IL-11 treatment diminished lung inflammation and reversed lung fibrosis while inhibiting ERK and SMAD activation in mice. These data prioritize IL-11 as a drug target for lung fibrosis and IPF.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248616	Interleukin-11 from mouse			Price

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