Therapy Targeting IL-13 Reduces Radiation-induced Lung Fibrosis in Mice

Therapy Targeting IL-13 Reduces Radiation-induced Lung Fibrosis in Mice
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Researchers identified a specific cytokine called interleukin-13 (IL-13) as a critical mediator of radiation lung injury, and provided evidence that therapeutic targeting of IL-13 may significantly lessen radiation-induced pulmonary fibrosis.

The study, “IL-13 is a therapeutic target in radiation lung injury,” was published in the journal Scientific Reports.

Patients who undergo thoracic irradiation (as a treatment for breast or thoracic malignancies, for example) may incur pulmonary fibrosis, which constitutes a potentially lethal adverse effect. The pro-fibrotic and pro-inflammatory cytokines TGF-β, IL-1β, and IL-6 have previously been suggested to mediate fibrosis after exposure to irradiation. However, the role of other cytokines, primarily those defined as type 2 cytokines, in promoting radiation lung injury remained unknown. Cytokines are small proteins that are secreted by specific cells of the immune system and affect cellular behavior and interactions between cells.

A team of researchers investigated the role of type 2 cytokines, particularly IL-13, in fibrotic progression after radiation-induced lung injury. These cytokines, including IL-13, have been identified as key factors contributing to fibrotic responses to injury.

Researchers used normal, wild-type mice and IL-13-deficient mice (“knock-out” mice for IL-13). They then analyzed the progression of radiation-induced pulmonary fibrosis and inflammation in irradiated lung tissue in control mice compared to IL-13-deficient mice.

Following irradiation, control mice showed an accumulation of activated immune cells, called macrophages, displaying high levels of IL-13 (denoting a type 2 inflammation response in irradiated mouse lungs). These changes were accompanied by extensive fibrosis. In comparison, IL-13 deficient mice showed no signs of these alterations. In fact, researchers observed that a lack of IL-13 protected mice from radiation-induced pulmonary fibrosis and against lethal radiation lung injury.

These results suggested IL-13 as a key triggering factor of radiation lung fibrosis.

Researchers then investigated the mechanism by which IL-13 drives lung fibrosis. They found that IL-13 promotes lung infiltration by activated macrophages following irradiation. They also observed that IL-13 promoted the expression of fibrosis-associated genes in irradiated lung tissue, including TGF-β, a major participant in fibrosis.

Therapeutic targeting of IL-13 with neutralizing antibodies resulted in a marked reduction in fibrosis in mice.

Taken together, the results support a major role for IL-13 as a regulator of radiation-induced lung injury, and show that anti-IL-13 therapeutics may prove beneficial when delivered in a timely fashion to patients with radiation-induced lung fibrosis.

Patricia holds a Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She has also served as a PhD student research assistant at the Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds a Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She has also served as a PhD student research assistant at the Department of Microbiology & Immunology, Columbia University, New York.
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