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.
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