Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury

Clare Eglin*, Jennifer Anne Wright, Ant Shepherd, Heather Massey, Sarah Hollis, Jonathan Towse, John Young, Matthew Maley, Stephen Bailey, Chris Wilkinson, Hugh Montgomery, Mike Tipton

*Corresponding author for this work

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Plasma biomarkers of inflammation, oxidative stress, endothelial function and damage were examined in 16 individuals with chronic NFCI (NFCI) and matched controls with (COLD, n = 17) or without (CON, n = 14) previous cold exposure.

Venous blood samples were collected at baseline to assess plasma biomarkers of endothelial function (nitrate, nitrite and endothelin-1), inflammation (interleukin-6 [IL-6], IL-10, tumour necrosis factor alpha and E-selectin), oxidative stress (protein carbonyl, 4-hydroxynonenal [4-HNE], superoxide dismutase [SOD] and nitrotyrosine) and endothelial damage (von Willebrand factor, syndecan-1 and tissue type plasminogen activator [TTPA]). Immediately following whole-body heating and separately, foot cooling, blood samples were taken for measurement of plasma [nitrate], [nitrite], [endothelin-1], [IL-6], [4-HNE] and [TTPA].

At baseline, [IL-10] and [syndecan-1] were increased in NFCI (P < 0.001 and P = 0.015 respectively) and COLD (P = 0.033 and P = 0.030) compared to CON. [4-HNE] was elevated in CON compared to both NFCI (P = 0.002) and COLD (P < 0.001). [Endothelin-1] was elevated in NFCI compared to COLD (P < 0.001) post-heating. [4-HNE] was lower in NFCI compared to CON post-heating (P = 0.032) and lower than both COLD (P = 0.02) and CON (P = 0.015) post-cooling. No between group differences were seen for the other biomarkers.

Mild to moderate chronic NFCI does not appear to be associated with a pro-inflammatory state or oxidative stress. Baseline [IL-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosing NFCI, however it is likely a combination of tests will be required.
Original languageEnglish
Pages (from-to)448-464
Number of pages17
JournalExperimental Physiology
Issue number3
Early online date20 Feb 2023
Publication statusPublished - 1 Mar 2023


  • cold injury
  • endothelial function
  • endothelin
  • interleukin
  • nitric oxide
  • oxidative stress
  • pathophysiology
  • syndecan

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