title: IL-13 is a therapeutic target in radiation lung injury.
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.
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Su I
authors.initials: SI
authors.lastname: Chung
authors.affiliation: Musculoskeletal Science Research Center, Dept. of Orthopedic Surgery, Upstate Medical University, Syracuse, New York, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Horton
authors.affiliation: Biomarker Discovery OMNI, Genentech, Inc. MS 231c, 1 DNA way, San Francisco, CA 94080 USA.
authors.forename: Thirumalai R
authors.initials: TR
authors.lastname: Ramalingam
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ayla O
authors.initials: AO
authors.lastname: White
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Chung
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hudak
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Scroggins
authors.affiliation: Biomarker Discovery OMNI, Genentech, Inc. MS 231c, 1 DNA way, San Francisco, CA 94080 USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Arron
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 4 Memorial Drive, Room 211C, Bethesda, MD 20892-0425, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wynn
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Citrin
mesh_terms: D000818:Animals; D018793:Interleukin-13 / Q000494:pharmacology*; D055370:Lung Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D011833:Radiation Injuries, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
chemical_list: D018793:Interleukin-13