IL-13 is a therapeutic target in radiation lung injury

Sci Rep. 2016 Dec 22;6:39714. doi: 10.1038/srep39714.

Abstract

Pulmonary fibrosis is a potentially lethal late adverse event of thoracic irradiation. Prior research indicates that unrestrained TGF-β1 and/or type 2 cytokine-driven immune responses promote fibrosis following radiation injury, but the full spectrum of factors governing this pathology remains unclear. Interleukin 13 (IL-13) is a key factor in fibrotic disease associated with helminth infection, but it is unclear whether it plays a similar role in radiation-induced lung fibrosis. Using a mouse model, we tested the hypothesis that IL-13 drives the progression of radiation-induced pulmonary fibrosis. Irradiated lungs from wild-type c57BL/6NcR mice accumulated alternatively-activated macrophages, displayed elevated levels of IL-13, and extensive fibrosis, whereas IL-13 deficient mice were resistant to these changes. Furthermore, plasma from irradiated wild-type mice showed a transient increase in the IL-13 saturated fraction of the circulating decoy receptor IL-13Rα2. Finally, we determined that therapeutic neutralization of IL-13, during the period of IL-13Rα2 saturation was sufficient to protect mice from lung fibrosis. Taken together, our results demonstrate that IL-13 is a major regulator of radiation-induced lung injury and demonstrates that strategies focusing on IL-13 may be useful in screening for timely delivery of anti-IL-13 therapeutics.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Interleukin-13 / pharmacology*
  • Lung Injury* / immunology
  • Lung Injury* / pathology
  • Lung Injury* / prevention & control
  • Mice
  • Mice, Knockout
  • Pulmonary Fibrosis* / immunology
  • Pulmonary Fibrosis* / pathology
  • Pulmonary Fibrosis* / prevention & control
  • Radiation Injuries, Experimental* / immunology
  • Radiation Injuries, Experimental* / pathology
  • Radiation Injuries, Experimental* / prevention & control

Substances

  • Interleukin-13