Large scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome
Abstract The specific cytokines that regulate pediatric acute respiratory distress syndrome (PARDS) pathophysiology remains unclear. Here, we evaluated the respiratory cytokine profile in PARDS to identify the molecular signatures associated with severe disease. A multiplex suspension immunoassay wa...
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Nature Portfolio
2021
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oai:doaj.org-article:823f3e2843cb4bb1923fd90646dd85e92021-12-02T16:15:06ZLarge scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome10.1038/s41598-021-93705-82045-2322https://doaj.org/article/823f3e2843cb4bb1923fd90646dd85e92021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93705-8https://doaj.org/toc/2045-2322Abstract The specific cytokines that regulate pediatric acute respiratory distress syndrome (PARDS) pathophysiology remains unclear. Here, we evaluated the respiratory cytokine profile in PARDS to identify the molecular signatures associated with severe disease. A multiplex suspension immunoassay was used to profile 45 cytokines, chemokines and growth factors. Cytokine concentrations were compared between severe and non-severe PARDS, and correlated with oxygenation index (OI). Partial least squares regression modelling and regression coefficient plots were used to identify a composite of key mediators that differentially segregated severe from non-severe disease. The mean (standard deviation) age and OI of this cohort was 5.2 (4.9) years and 17.8 (11.3), respectively. Early PARDS patients with severe disease exhibited a cytokine signature that was up-regulated for IL-12p70, IL-17A, MCP-1, IL-4, IL-1β, IL-6, MIP-1β, SCF, EGF and HGF. In particular, pro-inflammatory cytokines (IL-6, MCP-1, IP-10, IL-17A, IL-12p70) positively correlated with OI early in the disease. Whereas late PARDS was characterized by a differential lung cytokine signature consisting of both up-regulated (IL-8, IL-12p70, VEGF-D, IL-4, GM-CSF) and down-regulated (IL-1β, EGF, Eotaxin, IL-1RA, and PDGF-BB) profiles segregating non-severe and severe groups. This cytokine signature was associated with increased transcription, T cell activation and proliferation as well as activation of mitogen-activated protein kinase pathway that underpin PARDS severity.Judith Ju Ming WongHerng Lee TanJieliang ZhouJan Hau LeeJing Yao LeongJoo Guan YeoYie Hou LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Judith Ju Ming Wong Herng Lee Tan Jieliang Zhou Jan Hau Lee Jing Yao Leong Joo Guan Yeo Yie Hou Lee Large scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome |
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Abstract The specific cytokines that regulate pediatric acute respiratory distress syndrome (PARDS) pathophysiology remains unclear. Here, we evaluated the respiratory cytokine profile in PARDS to identify the molecular signatures associated with severe disease. A multiplex suspension immunoassay was used to profile 45 cytokines, chemokines and growth factors. Cytokine concentrations were compared between severe and non-severe PARDS, and correlated with oxygenation index (OI). Partial least squares regression modelling and regression coefficient plots were used to identify a composite of key mediators that differentially segregated severe from non-severe disease. The mean (standard deviation) age and OI of this cohort was 5.2 (4.9) years and 17.8 (11.3), respectively. Early PARDS patients with severe disease exhibited a cytokine signature that was up-regulated for IL-12p70, IL-17A, MCP-1, IL-4, IL-1β, IL-6, MIP-1β, SCF, EGF and HGF. In particular, pro-inflammatory cytokines (IL-6, MCP-1, IP-10, IL-17A, IL-12p70) positively correlated with OI early in the disease. Whereas late PARDS was characterized by a differential lung cytokine signature consisting of both up-regulated (IL-8, IL-12p70, VEGF-D, IL-4, GM-CSF) and down-regulated (IL-1β, EGF, Eotaxin, IL-1RA, and PDGF-BB) profiles segregating non-severe and severe groups. This cytokine signature was associated with increased transcription, T cell activation and proliferation as well as activation of mitogen-activated protein kinase pathway that underpin PARDS severity. |
format |
article |
author |
Judith Ju Ming Wong Herng Lee Tan Jieliang Zhou Jan Hau Lee Jing Yao Leong Joo Guan Yeo Yie Hou Lee |
author_facet |
Judith Ju Ming Wong Herng Lee Tan Jieliang Zhou Jan Hau Lee Jing Yao Leong Joo Guan Yeo Yie Hou Lee |
author_sort |
Judith Ju Ming Wong |
title |
Large scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome |
title_short |
Large scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome |
title_full |
Large scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome |
title_fullStr |
Large scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome |
title_full_unstemmed |
Large scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome |
title_sort |
large scale cytokine profiling uncovers elevated il12-p70 and il-17a in severe pediatric acute respiratory distress syndrome |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/823f3e2843cb4bb1923fd90646dd85e9 |
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