Format

Send to

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

IL-13 is a therapeutic target in radiation lung injury.

Author information

1
Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
2
Musculoskeletal Science Research Center, Dept. of Orthopedic Surgery, Upstate Medical University, Syracuse, New York, USA.
3
Biomarker Discovery OMNI, Genentech, Inc. MS 231c, 1 DNA way, San Francisco, CA 94080 USA.
4
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 4 Memorial Drive, Room 211C, Bethesda, MD 20892-0425, USA.

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.

PMID:
28004808
PMCID:
PMC5177927
DOI:
10.1038/srep39714
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center