Progress in the mechanism of radiation-induced lung injury

Ying, Hangjie; Fang, Min; Chen, Ming

doi:10.1097/cm9.0000000000001032

Cited by 10 publications

(7 citation statements)

References 19 publications

(8 reference statements)

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“…Macrophages play pro-inflammatory and anti-inflammatory roles through classical and alternative activation pathways, Which we refer to the polarized macrophages as M1 and M2 ( 28 ). The former is characterized by inducible nitric oxide synthase, and the latter is marked by arginase-1.…”

Section: Immunomodulatory Mechanisms Of Azithromycinmentioning

confidence: 99%

Immunomodulatory role of azithromycin: Potential applications to radiation-induced lung injury

Yan

Wu²,

Li³

et al. 2023

Front. Oncol.

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Radiation-induced lung injury (RILI) including radiation-induced pneumonitis and radiation-induced pulmonary fibrosis is a side effect of radiotherapy for thoracic tumors. Azithromycin is a macrolide with immunomodulatory properties and anti-inflammatory effects. The immunopathology of RILI that results from irradiation is robust pro-inflammatory responses with high levels of chemokine and cytokine expression. In some patients, pulmonary interstitial fibrosis results usually due to an overactive immune response. Growing clinical studies recently proposed that the anti-inflammatory and immunomodulatory effects of azithromycin may benefit patients with acute lung injury. It has been shown potential benefits for patients with RILI in preclinical studies. Azithromycin has a variety of immunomodulatory effect to improve the process of disease, including inhibition of pro-inflammatory cytokines production participating in the regulatory function of macrophages, changes in autophagy, and inhibition of neutrophil influx. We review the published evidence of mechanisms of azithromycin, and focus on the potential effect of azithromycin on the immune response to RILI.

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Section: Immunomodulatory Mechanisms Of Azithromycinmentioning

confidence: 99%

Immunomodulatory role of azithromycin: Potential applications to radiation-induced lung injury

Yan

Wu²,

Li³

et al. 2023

Front. Oncol.

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“…19–22 The FDA approved pirfenidone in 2014 for the treatment of idiopathic pulmonary fibrosis (IPF), 23 24 which shares some pathological manifestations with RILI. 25 26 A previous study in mice showed that pirfenidone attenuates RILI. 27 A phase 2 trial is in the recruitment stage and aims to confirm the efficacy of pirfenidone in the treatment of RILI (ClinicalTrials.gov, NCT03902509).…”

Section: Introductionmentioning

confidence: 99%

“…Pharmacodynamic studies have demonstrated pirfenidone exerts satisfactory effects in lung inflammation and fibrosis 19–22. The FDA approved pirfenidone in 2014 for the treatment of idiopathic pulmonary fibrosis (IPF),23 24 which shares some pathological manifestations with RILI 25 26. A previous study in mice showed that pirfenidone attenuates RILI 27.…”

Section: Introductionmentioning

confidence: 99%

Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial

et al. 2022

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IntroductionRadiation-induced lung injury (RILI) is one of the most clinically-challenging toxicities and dose-limiting factors during and/or after thoracic radiation therapy for oesophageal squamous cell carcinoma (ESCC). With limited effective protective drugs against RILI, the main strategy to reduce the injury is strict adherence to dose-volume restrictions of normal lungs. RILI can manifest as acute radiation pneumonitis with cellular injury, cytokine release and cytokine recruitment to inflammatory infiltrate, and subsequent chronic radiation pulmonary fibrosis. Pirfenidone inhibits the production of inflammatory cytokines, scavenges-free radicals and reduces hydroxyproline and collagen formation. Hence, pirfenidone might be a promising drug for RILI prevention. This study aims to evaluate the efficacy and safety of pirfenidone in preventing RILI in patients with locally advanced ESCC receiving chemoradiotherapy.Methods and analysisThis study is designed as a randomised, placebo-controlled, double-blinded, single-centre phase 2 trial and will explore whether the addition of pirfenidone during concurrent chemoradiation therapy (CCRT) could prevent RILI in patients with locally advanced ESCC unsuitable for surgery. Eligible participants will be randomised at 1:1 to pirfenidone and placebo groups. The primary endpoint is the incidence of grade >2 RILI. Secondary endpoints include the incidence of any grade other than grade >2 RILI, time to RILI occurrence, changes in pulmonary function after CCRT, completion rate of CCRT, disease-free survival and overall survival. The follow-up period will be 1 year. In case the results meet the primary endpoint of this trial, a phase 3 multicentre trial with a larger sample size will be required to substantiate the evidence of the benefit of pirfenidone in RILI prevention.Ethics and disseminationThis study was approved by the Ethics Committee of Fujian Union Hospital (No. 2021YF001-02). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations.Trial registration numberChiCTR2100043032.

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“…Radiation treatment has been shown to increase the population of infiltrating lymphocytes in lung tissue, resulting in lymphocytic alveolitis, which is closely related to lymphocyte-mediated immune responses. 6 , 7 Activation of T lymphocytes by PD-1 inhibitors can mediate immune pneumonitis, with an incidence of about 20%. 8 , 9 Because lung injuries caused by both radiotherapy and PD-1 inhibitors are associated with T-cell-mediated immune-inflammatory responses, the combination of radiotherapy and PD-1 inhibitors may exacerbate lung injury.…”

Section: Introductionmentioning

confidence: 99%

Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice

Geng¹,

Su²,

Cao³

et al. 2022

JIR

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Purpose This study was designed to evaluate the effects of PD-1 inhibitor on lung tissue morphology and the immune system in a mouse model of radiation-induced lung injury (RILI) and to assess interactions between radiation therapy and PD-1 inhibition. Methods Twenty C57BL/6 mice were divided randomly into four groups of five mice each. Mice were treated with an anti-mouse PD-1 monoclonal antibody, whole thorax irradiation, both or neither. Lung tissue morphology and pathological changes were assessed by hematoxylin-eosin staining; lung fibrosis was assessed by Masson staining and analysis of hydroxyproline; CD3+, CD4+, and CD8+ T lymphocytes in lung tissues were detected immunohistochemically; and the concentrations of transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6) in lung tissue were evaluated by cytokine multiplex analysis. Results Lung injury scores and indicators of pulmonary fibrosis were higher in mice administration whole thorax irradiation than in control mice. Inflammatory infiltrate scores, alveoli deformation scores, collagen volume fractions and hydroxyproline contents in lung tissues were all significantly higher in mice administered PD-1 inhibitor plus irradiation than in the other three groups. Similarly, the percentages of CD3+ and CD8+T cells and the concentrations of IL-6 and TGF-β1 in lung tissue were significantly higher in mice treated with radiation and PD-1 inhibitor than in the other groups. However, PD-1 inhibitor and irradiation interacted significantly only in the elevation of TGF-β1 level. Conclusion Whole thorax X-ray irradiation in mice can cause pulmonary injury and fibrosis, which could be exacerbated by PD-1 inhibitors. Radiotherapy combined with PD-1 inhibitors may aggravate RILI by synergistically upregulating TGF-β1 expression, thereby affecting the immune-inflammatory microenvironment in the lungs.

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Progress in the mechanism of radiation-induced lung injury

Cited by 10 publications

References 19 publications

Immunomodulatory role of azithromycin: Potential applications to radiation-induced lung injury

Immunomodulatory role of azithromycin: Potential applications to radiation-induced lung injury

Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial

Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice

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