Research ArticleIdiopathic Pulmonary Fibrosis

Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis

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Science Translational Medicine  25 Sep 2019:
Vol. 11, Issue 511, eaaw1237
DOI: 10.1126/scitranslmed.aaw1237

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Targeting IL-11 in lung fibrosis

In idiopathic pulmonary fibrosis (IPF), chronic activation of invasive fibroblasts is responsible for fibrotic scar formation in the lungs. Patients with IPF present progressive difficulty to breathe, pulmonary hypertension, and respiratory failure. The pathophysiological mechanisms remain unclear. Interleukin-11 (IL-11) has been shown to participate in kidney and cardiac fibrosis. However, conflicting data suggest that IL-11 can either be pro- or antifibrotic. Now, Ng et al. reported that in patients with IPF, IL-11 was up-regulated in invasive lung fibroblasts. In vitro and in vivo experiments demonstrated that IL-11 exerted profibrotic effects by driving fibroblast activation. Targeting IL-11 with a neutralizing antibody had therapeutic effects in a mouse model of established pulmonary fibrosis.


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.

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