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Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS)

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. DESIGN, SETTING, AND SUBJECTS: Blood...

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Autores principales: Monaghan, Sean F., Chung, Chun-Shiang, Chen, Yaping, Lomas-Neira, Joanne, Fairbrother, William G., Heffernan, Daithi S., Cioffi, William G., Ayala, Alfred
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106799/
https://www.ncbi.nlm.nih.gov/pubmed/27835962
http://dx.doi.org/10.1186/s12967-016-1071-x
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author Monaghan, Sean F.
Chung, Chun-Shiang
Chen, Yaping
Lomas-Neira, Joanne
Fairbrother, William G.
Heffernan, Daithi S.
Cioffi, William G.
Ayala, Alfred
author_facet Monaghan, Sean F.
Chung, Chun-Shiang
Chen, Yaping
Lomas-Neira, Joanne
Fairbrother, William G.
Heffernan, Daithi S.
Cioffi, William G.
Ayala, Alfred
author_sort Monaghan, Sean F.
collection PubMed
description BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. DESIGN, SETTING, AND SUBJECTS: Blood and bronchial alveolar lavage fluid (BAL) from humans (n = 10–13) with ARDS and controls (n = 5–10) as well as a murine model of ARDS (n = 5–6) with controls (n = 6–7) were studied. METHODS: ARDS was induced in mice by hemorrhagic shock (day 1) followed by poly-microbial sepsis (day 2). Samples were then collected on the third day after the animals were euthanized. Ex vivo experiments used splenocytes from animals with ARDS cultured with and without soluble programmed death receptor-1 (sPD-1). RESULTS: Levels of sPD-1 are increased in both the serum (11,429.3 pg/mL(SD 2133.3) vs. 8061.4(SD 4187.8), p = 0.036) and bronchial alveolar lavage (BAL) fluid (6,311.1 pg/mL(SD 3758.0) vs. 90.7 pg/mL(SD 202.8), p = 0.002) of humans with ARDS. Similar results are seen in the serum (9396.1 pg/mL(SD 1546.0) vs. 3464.5 pg/mL(SD 2511.8), p = 0.001) and BAL fluid (2891.7 pg/mL(SD 868.1) vs. 1385.9 pg/mL(SD 927.8), p = 0.012) of mice. sPD-1 levels in murine blood (AUC = 1(1–1), p = 0.006), murine BAL fluid (AUC = 0.905(0.717–1.093), p = 0.015), and human BAL (AUC = 1(1–1), p = 0.001) fluid predicted ARDS. To assess the importance of sPD-1 in ARDS, ex vivo experiments were undertaken. BAL fluid from mice with ARDS dampens the TNF-α production compared to cells cultured with BAL lacking sPD-1 (2.7 pg/mL(SD 3.8) vs. 52.38 pg/mL(SD 25.1), p = 0.002). CONCLUSIONS: This suggests sPD-1 is elevated in critical illness and may represent a potential biomarker for ARDS. In addition, sPD-1 has an anti-inflammatory mechanism in conditions of marked stress and aids in the resolution of severe inflammation. sPD-1 could be used to not only diagnose ARDS, but may be a potential therapy.
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spelling pubmed-51067992016-11-21 Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS) Monaghan, Sean F. Chung, Chun-Shiang Chen, Yaping Lomas-Neira, Joanne Fairbrother, William G. Heffernan, Daithi S. Cioffi, William G. Ayala, Alfred J Transl Med Research BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a common organ dysfunction in the critically ill patient. Mechanisms for its development have focused on immune mediated causes, aspects of our understanding are not complete, and we lack biomarkers. DESIGN, SETTING, AND SUBJECTS: Blood and bronchial alveolar lavage fluid (BAL) from humans (n = 10–13) with ARDS and controls (n = 5–10) as well as a murine model of ARDS (n = 5–6) with controls (n = 6–7) were studied. METHODS: ARDS was induced in mice by hemorrhagic shock (day 1) followed by poly-microbial sepsis (day 2). Samples were then collected on the third day after the animals were euthanized. Ex vivo experiments used splenocytes from animals with ARDS cultured with and without soluble programmed death receptor-1 (sPD-1). RESULTS: Levels of sPD-1 are increased in both the serum (11,429.3 pg/mL(SD 2133.3) vs. 8061.4(SD 4187.8), p = 0.036) and bronchial alveolar lavage (BAL) fluid (6,311.1 pg/mL(SD 3758.0) vs. 90.7 pg/mL(SD 202.8), p = 0.002) of humans with ARDS. Similar results are seen in the serum (9396.1 pg/mL(SD 1546.0) vs. 3464.5 pg/mL(SD 2511.8), p = 0.001) and BAL fluid (2891.7 pg/mL(SD 868.1) vs. 1385.9 pg/mL(SD 927.8), p = 0.012) of mice. sPD-1 levels in murine blood (AUC = 1(1–1), p = 0.006), murine BAL fluid (AUC = 0.905(0.717–1.093), p = 0.015), and human BAL (AUC = 1(1–1), p = 0.001) fluid predicted ARDS. To assess the importance of sPD-1 in ARDS, ex vivo experiments were undertaken. BAL fluid from mice with ARDS dampens the TNF-α production compared to cells cultured with BAL lacking sPD-1 (2.7 pg/mL(SD 3.8) vs. 52.38 pg/mL(SD 25.1), p = 0.002). CONCLUSIONS: This suggests sPD-1 is elevated in critical illness and may represent a potential biomarker for ARDS. In addition, sPD-1 has an anti-inflammatory mechanism in conditions of marked stress and aids in the resolution of severe inflammation. sPD-1 could be used to not only diagnose ARDS, but may be a potential therapy. BioMed Central 2016-11-11 /pmc/articles/PMC5106799/ /pubmed/27835962 http://dx.doi.org/10.1186/s12967-016-1071-x Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Monaghan, Sean F.
Chung, Chun-Shiang
Chen, Yaping
Lomas-Neira, Joanne
Fairbrother, William G.
Heffernan, Daithi S.
Cioffi, William G.
Ayala, Alfred
Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS)
title Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS)
title_full Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS)
title_fullStr Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS)
title_full_unstemmed Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS)
title_short Soluble programmed cell death receptor-1 (sPD-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ARDS)
title_sort soluble programmed cell death receptor-1 (spd-1): a potential biomarker with anti-inflammatory properties in human and experimental acute respiratory distress syndrome (ards)
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106799/
https://www.ncbi.nlm.nih.gov/pubmed/27835962
http://dx.doi.org/10.1186/s12967-016-1071-x
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