Inflammatory cytokines have been suggested to play important roles in radiation-induced lung injury (RILI). Identifying significantly changed circulating and tissue cytokines after thoracic irradiation will aid in deciphering the mechanism of RILI and identifying potential biomarkers to predict clinical outcome. Herein, the levels of 24 cytokines were measured in serial plasma samples and lung tissue samples collected from a pilot study where nonhuman primates (NHPs) received 11.5 Gy whole thoracic lung irradiation (WTLI) and were then treated with or without a medical countermeasure, AEOL 10150 [a superoxide dismutase (SOD) mimetic]. Seven plasma cytokines (i.e., IP-10, MCP-1, IL-12, IL-15, IL-16, IL-7 and IL-6) were found to be significantly changed at different time points due to WTLI. Plasma IP-10 and MDC were significantly changed between the vehicle group and the drug group. The levels of IP-10, MCP-1, MIP-1α, TARC, IL-17, TNF-β and IL-6 were significantly elevated in the lung tissue lysates of NHPs that received WTLI versus radiation-naïve NHPs. The terminal plasma concentrations of IP-10, MDC, TARC, IL-12, IL-15 and IL-6 were significantly correlated with their levels in the lung tissue. The levels of four cytokines (MCP-4, IL-17, TNF-β and IL-2) at early time points (≤8 weeks postirradiation) were significantly correlated with their terminal plasma levels, respectively. Statistical analysis indicated that circulating cytokines could be discriminatory predictors of AEOL 10150 treatment. Taken together, our data suggested that the cytokine profiles were significantly changed after WTLI as well as mitigator treatment, and that the plasma cytokine profiles could potentially be used to distinguish vehicle or mitigator treatment after WTLI in a NHP model.
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July 2020
Research Article|
April 30 2020
Identifying Circulating and Lung Tissue Cytokines Associated with Thoracic Irradiation and AEOL 10150 Treatment in a Nonhuman Primate Model
Wanchang Cui;
Wanchang Cui
1,
a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889
b Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201
Radiaiton Research Society, Scholar-in-Training.
1 Address for correspondence: 4555 South Palmer Road, Bldg. 45, Room 3319, Bethesda, MD 20889; Email: wanchang.cui.ctr@usuhs.edu; or tmacvittie@som.umaryland.edu.
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Kim G. Hankey;
Kim G. Hankey
b Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201
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Pei Zhang;
Pei Zhang
b Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201
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David L. Bolduc;
David L. Bolduc
a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889
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Rolf Bünger;
Rolf Bünger
c Department of Consultant, McLean, Virginia
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Mang Xiao;
Mang Xiao
a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889
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Ann M. Farese;
Ann M. Farese
b Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201
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Thomas J. MacVittie
Thomas J. MacVittie
1
b Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201
1 Address for correspondence: 4555 South Palmer Road, Bldg. 45, Room 3319, Bethesda, MD 20889; Email: wanchang.cui.ctr@usuhs.edu; or tmacvittie@som.umaryland.edu.
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Radiat Res (2020) 194 (1): 81–88.
Article history
Received:
November 02 2015
Accepted:
April 09 2020
Citation
Wanchang Cui, Kim G. Hankey, Pei Zhang, David L. Bolduc, Rolf Bünger, Mang Xiao, Ann M. Farese, Thomas J. MacVittie; Identifying Circulating and Lung Tissue Cytokines Associated with Thoracic Irradiation and AEOL 10150 Treatment in a Nonhuman Primate Model. Radiat Res 8 July 2020; 194 (1): 81–88. doi: https://doi.org/10.1667/RR14310.1
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