Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis

Sci Transl Med. 2019 Sep 25;11(511):eaaw1237. doi: 10.1126/scitranslmed.aaw1237.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / pharmacology
  • Antibodies, Neutralizing / therapeutic use
  • Bleomycin
  • Fibroblasts / pathology
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Idiopathic Pulmonary Fibrosis / pathology
  • Interleukin-11 / therapeutic use*
  • Interleukin-11 Receptor alpha Subunit / metabolism
  • Lung / pathology
  • Mice, Knockout
  • Severity of Illness Index
  • Signal Transduction
  • Up-Regulation


  • Antibodies, Neutralizing
  • Il11ra1 protein, mouse
  • Interleukin-11
  • Interleukin-11 Receptor alpha Subunit
  • Bleomycin