Acute Radiation-induced Lung Injury Research Articles

Detection of the serum endothelin content in patients with acute lung injury and its value of severity evaluation

ObjectiveTo observe the correlation of serum endothelin content in patients with acute radiation lung injury and with the degree of inflammatory reaction and the lung functional level. Methods68 Patients with non-small cell lung cancer who received the radiotherapy in treatment from May 2013 to October 2015 in our hospital were selected as the object of study. 25 patients who had acute radiation induced lung injury within 24 months of the radiotherapy were rolled in the radiation induced lung injury group (RILI group), and the rest of 43 without acute lung injury were rolled in the negative control group (NC group). The contents of endothelin, tumor necrosis factor α, interleukin-1β, interleukin-6 in serum and the partial pressure of oxygen in artery, partial pressure of carbon dioxide in artery, vital capacity, forced expiratory volume in one second, maximal ventilatory volume, and diffusion capacity for carbon monoxide were tested. ResultsThe content of serum endothelin of the patients in the RILI group [(69.3 ± 7.5) pg/mL] were all obviously higher than that of the NC group [(24.1 ± 2.9) pg/mL]; the content of the serum tumor necrosis factor α [(49.6 ± 5.1) ng/mL vs. (22.7 ± 3.1) ng/mL], interleukin-1β [(29.4 ± 3.3) ng/mL vs. (15.7 ± 1.8) ng/mL], interleukin-6 [(163.4 ± 20.3) pg/mL vs. (89.4 ± 10.2) pg/mL] and the partial pressure of carbon dioxide in artery [(49.2 ± 5.2) mmHg vs. (40.3 ± 4.8) mmHg] were all obviously higher than that of the NC group, which were positively correlated with the serum endothelin content. But the partial pressure of oxygen in artery [(68.4 ± 7.8) mmHg vs. (87.3 ± 9.5) mmHg], vital capacity [(1203.4 ± 136.5) mL vs. (2034.8 ± 238.5) mL], forced expiratory volume in one second [(38.4 ± 4.1)% vs. (58.3 ± 6.2)%], maximum minute ventilation [(33.7 ± 3.8) L/min vs. (66.1 ± 7.9) L/min] and diffusing capacity of the lungs for carbon monoxide [(79.3 ± 8.9)% vs. (86.7 ± 9.4)%)] were obviously lower than that of the NC group, which were negatively correlated with the serum endothelin content. ConclusionThe elevated content of the endothelin in the serum of patients with acute radiation induced lung injury could assess the degree of inflammatory reaction and the lung functional level.

Effects of CpG oligodeoxynucleotide 1826 on acute radiation-induced lung injury in mice.

BackgroundThe radiation-induced lung injury is a common complication from radiotherapy in lung cancer. CpG ODN is TLR9 activator with potential immune modulatory effects and sensitization of radiotherapy in lung cancer. This study aimed to examine the effect of CpG ODN on acute radiation-induced lung injury in mice.Methods and resultsThe mouse model of radiation-induced lung injury was established by a single dose of 20 Gy X-rays exposure to the left lung. The results showed that the pneumonia score was lower in RT+CpG group than in RT group on 15th and 30th days. Compared with RT group, CpG ODN reduced the serum concentrations of MDA (P < 0.05) and increased the serum concentrations of SOD, GSH (P < 0.05). The serum concentration of TNF-α in RT+CpG group was lower on 15th and 30th days post-irradiation (P < 0.05).ConclusionThe study demonstrated that CpG ODN has preventive effects of acute radiation-induced lung injury in mice. Lung inflammatory reaction and oxidative stress are promoted in the initiation of radiation-induced pneumonia. CpG ODN may reduce the injury of reactive oxygen species and adjust the serum TNF-α concentration in the mice after irradiation, which reduces the generation of the inflammatory cytokines.

Factors related to severe acute radiation-induced lung injury caused by IMRT for nonsmall cell lung cancer

Factors related to severe acute radiation-induced lung injury caused by IMRT for nonsmall cell lung cancer

Intravenous delivery of adipose-derived mesenchymal stromal cells attenuates acute radiation-induced lung injury in rats

Background aimsRadiation-induced lung injury (RILI) commonly occurs in patients with thoracic cancer. However, an effective treatment option has not yet been established. Adipose-derived mesenchymal stromal cells (Ad-MSCs) have significant potential for clinical use, but their role in RILI is currently unknown. We aimed to evaluate the therapeutic capacity of Ad-MSCs to heal acute RILI in rats. MethodsSprague-Dawley rats were used in this study. Rat Ad-MSCs were delivered through the tail veins of rats 2 h after thorax irradiation. Lung histopathologic findings, pulmonary levels of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-10 and tumor necrosis factor-α), pro-fibrotic factors (transforming growth factor [TGF]-β1, connective tissue growth factor, α-smooth muscle actin and type 1 collagen), pro- or anti-apoptotic mediators (Bcl-2, Bax and caspase-3) and the multifunctional factor hepatocyte growth factor were evaluated after Ad-MSC transplant. ResultsIntravenous delivery of Ad-MSCs attenuated acute RILI. Further studies showed that Ad-MSCs had anti-inflammation and anti-fibrotic effects and maintained lung epithelium integrity, as indicated by reduced serum levels of the pro-inflammatory cytokines IL-1, IL-6 and tumor necrosis factor-α, increased levels of the anti-inflammatory cytokine IL-10, and downregulated transforming growth factor -β1, α-smooth muscle actin and type 1 collagen levels in irradiated lung tissues. Ad-MSCs also regulated the expression of pro- and anti-apoptotic mediators (Bcl-2, Bax and caspase-3) to protect lung cells from apoptosis. ConclusionsIntravenous Ad-MSC delivery attenuated acute RILI through anti-inflammation, anti-fibrosis and anti-apoptosis mechanisms.

A preclinical rodent model of acute radiation-induced lung injury after ablative focal irradiation reflecting clinical stereotactic body radiotherapy.

In a previous study, we established an image-guided small-animal micro-irradiation system mimicking clinical stereotactic body radiotherapy (SBRT). The goal of this study was to develop a rodent model of acute phase lung injury after ablative irradiation. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice using a small animal stereotactic irradiator. At days 1, 3, 5, 7, 9, 11 and 14 after irradiation, the lungs were perfused with formalin for fixation and paraffin sections were stained with hematoxylin and eosin (H&E) and Masson's trichrome. At days 7 and 14 after irradiation, micro-computed tomography (CT) images of the lung were taken and lung functional measurements were performed with a flexiVent™ system. Gross morphological injury was evident 9 days after irradiation of normal lung tissues and dynamic sequential events occurring during the acute phase were validated by histopathological analysis. CT images of the mouse lungs indicated partial obstruction located in the peripheral area of the left lung. Significant alteration in inspiratory capacity and tissue damping were detected on day 14 after irradiation. An animal model of radiation-induced lung injury (RILI) in the acute phase reflecting clinical stereotactic body radiotherapy was established and validated with histopathological and functional analysis. This model enhances our understanding of the dynamic sequential events occurring in the acute phase of radiation-induced lung injury induced by ablative dose focal volume irradiation.

Early detection of acute radiation-induced lung injury with multi-section CT perfusion imaging: An initial experience

To explore the value of 64-section computed tomography (CT) perfusion imaging (CTPI) in the early diagnosis of acute radiation-induced lung injury (ARILI). Fifty-one patients with oesophageal cancers or malignant thymomas received postoperative radiation therapy with a 60-62 Gy dose and underwent CTPI at pre- and post-radiation therapy time points (week 0, week 4, week 8, and week 12 respectively). The CTPI values were prospectively compared and analysed in order to evaluate the diagnostic utility of CTPI in the early diagnosis of ARILI. Eighteen cases (18/51) of ARILI were diagnosed. The mean values of relative regional blood flow (rrBF), relative regional volume (rrBV), and relative regional permeability surface (rrPS) in the ARILI group were correspondingly higher than those of the non-ARILI group. At week 4, rrBF, rrBV, and rrPS in the ARILI group were significantly higher than those at pre-radiation (each p < 0.05). In the non-ARILI group, rrBF and rrBV were higher than those at pre-radiation (each p < 0.05); however, rrPS was not statistically different from that of pre-irradiation. Applying the diagnostic threshold value of rrPS = 1.22, the sensitivity, specificity, and positive and negative predictive values of CTPI for early diagnosis of ARILI were better than those of CT. CTPI metrics may reflect haemodynamic changes in the post-irradiation lung and can detect cases of early ARILI that appear normal at CT. CTPI is a promising technique for early diagnosis of ARILI.

Protection against acute radiation-induced lung injury: A novel role for the anti-angiogenic agent Endostar

Radiotherapy is commonly used to treat thoracic malignancies, but often causes severe lung injury. Currently there are no effective protective strategies against radiation-induced lung injury (RILI). This study aimed to evaluate the ability of an angiogenesis antagonist, Endostar, against RILI, and the underlying mechanism in a mouse model. A total of 108 C57BL/6 female mice were randomized into 4 groups (n=27): i) control group; ii) Endostar group, animals were administered 7.75 ml/kg Endostar through intraperitoneal injection; iii) irradiation group, RILI was induced by exposing the animals to a single external irradiation on the thoraces (6 MV X-ray, 12 Gy); and iv) irradiation plus Endostar group, animals were subjected to Endostar treatment and irradiation as in groups 2 and 3. A total of 3 animals from each of the 4 groups were sacrificed at 1, 6, 12, 24 and 72 h and at 2, 4, 8 and 24 weeks following treatment. Clinical signs and pathology of RILI were examined. The expression of transforming growth factor-β 1 (TGF-β1) in lungs was analyzed by real-time quantitative polymerase chain reaction (RT-QPCR) and immunohistochemistry. Compared with the control group, irradiation induced evident interstitial edema and a significant increase in inflammatory cells in the lungs (P<0.05). Correlated with these changes, a notable increase in TGF-β1 mRNA level and a robust increase in TGF-β1 immunoreactivity were observed in lung tissues in a time-dependent manner following irradiation (P<0.05). Endostar administration effectively attenuated the magnitude of the increase in inflammatory cells as well as the elevation of TGF-β1 expression in lung tissues after RILI (P<0.05). In conclusion, radiation induced an increased expression of the inflammatory mediator TGF-β1 and the associated pathogenesis in the lung, while Endostar was able to at least partially attenuate RILI through downregulating the expression of TGF-β1 in mice. Our findings suggest that Endostar may be a novel protective agent against RILI.

Suppression by methylprednisolone of the expression of LFA-1 by alveolar macrophages in irradiated rat lungs

A common side effect of radiotherapy is the development of fibrosis in the irradiated tissue. To study the effects of methylprednisolone on acute radiation-induced lung injury, we counted neutrophils, lymphocytes, and macrophages, and measured the expression on alveolar macrophages of lymphocyte function associated molecule-1 (LFA-1) in bronchoalveolar lavage fluid recovered from irradiated rat lungs. Twenty 10-week-old male Wistar rats were divided into 4 groups of 5 rats each: (1) a radiation group (R), which received 20 Gy of radiation from 60Co to the left hemithorax in one fraction; (/) a methylprednisolone treatment group (RS), which received the same dose of radiation as the R group, along with 2.0 mg x kg-1 of methylprednisolone (6 alpha methylprednisolone 21-acetate) by intramuscular injection 6 hours before and every 48 hours after irradiation; (3) an untreated control group (C); and (4) a methylprednisolone control group (S), which received the same dosage of methylprednisolone as the RS group. Rats were kept under specific-pathogen-free conditions. Bronchoalveolar lavage of the left lung was done in all 4 groups 2 week after irradiation. The number of neutrophils in the recovered fluid was significantly higher in the R and RS groups than in the C and S groups. The expression of LFA-1 on alveolar macrophages was significantly higher in the R group than in the RS, C, and S groups. The number of neutrophils in bronchoalveolar lavage fluid and the expression of LFA-1 on alveolar macrophages were significantly higher in the R group than in the RS groups. These results suggest that the increase in the expression of LFA-1 on alveolar macrophages and the increase in the number of neutrophils in bronchoalveolar lavage fluid are related to acute radiation-induced lung injury. Methylprednisolone suppressed the expression of LFA-1 on alveolar macrophages and the increase in the number of neutrophils measured in bronchoalveolar lavage fluid 2 weeks after irradiation.

Soluble TGFβ TYPE II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats

Purpose To assess whether administration of recombinant human adenoviral vector, which carries soluble TGFβ1 Type II receptor (TβRII) gene, might reduce the availability of active TGFβ1 and thereby protect the lung from radiation-induced injury. Methods and materials Female Fisher 344 rats were given a single 30 Gy dose of right hemithoracic irradiation 24 h after the injections of control (AdGFP) or treatment (AdexTβRII-Fc) vectors. Different end points were assessed to look for lung tissue damage. Results There was a significant increase in the plasma level of soluble TβRII 24 h and 48 h after injection of treatment vector. In the radiation (RT) + AdexTβRII-Fc group, there was a significant reduction in respiratory rate at 4 weeks after treatment as compared to the RT-alone group. Histologic results revealed a significant reduction in lung damage and decrease in the number and activity of macrophages in the RT + AdexTβRII-Fc group as compared to the RT-alone group. The tissue level of active TGFβ1 was significantly reduced in rats receiving RT + AdexTβRII-Fc treatment. There was also an upregulation of transmembrane TβRII in lung tissue in the RT-alone group as compared to the RT + gene therapy rats. Conclusions This study shows the ability of AdexTβRII-Fc gene therapy to induce an increase in circulating levels of soluble receptors, to reduce the tissue level of active TGFβ1, and consequently to ameliorate acute radiation-induced lung injury.

Effect of Corticosteroid Treatment on Cell Recovery by Lung Lavage in Acute Radiation-Induced Lung Injury

The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.