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Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model.

Rocha-Ferreira, E; Kelen, D; Faulkner, S; Broad, KD; Chandrasekaran, M; Kerenyi, Á; Kato, T; ... Robertson, NJ; + view all (2017) Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model. J Neuroinflammation , 14 (1) p. 44. 10.1186/s12974-017-0821-x. Green open access

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Abstract

BACKGROUND: Inflammatory cytokines are implicated in the pathogenesis of perinatal hypoxia-ischemia (HI). The influence of hypothermia (HT) on cytokines after HI is unclear. Our aim was to assess in a piglet asphyxia model, under normothermic (NT) and HT conditions: (i) the evolution of serum cytokines over 48 h and (ii) cerebrospinal fluid (CSF) cytokine levels at 48 h; (iii) serum pro/anti-inflammatory cytokine profile over 48 h and (iv) relation between brain injury measured by magnetic resonance spectroscopy (MRS) and brain TUNEL positive cells with serum cytokines, serum pro/anti-inflammatory cytokines and CSF cytokines. METHODS: Newborn piglets were randomized to NT (n = 5) or HT (n = 6) lasting 2-26 h after HI. Serum samples were obtained 4-6 h before, during and at 6-12 h intervals after HI; CSF was obtained at 48 h. Concentrations of interleukin (IL)-1β, -4, -6, -8, -10 and TNF-α were measured and pro/anti-inflammatory status compared between groups. White matter and thalamic voxel lactate/N-acetyl aspartate (Lac/NAA) (a measure of both oxidative metabolism and neuronal loss) were acquired at baseline, after HI and at 24 and 36 h. RESULTS: Lac/NAA was reduced at 36 h with HT compared to NT (p = 0.013 basal ganglia and p = 0.033 white matter). HT showed lower serum TNF-α from baseline to 12 h (p < 0.05). Time-matched (acquired within 5 h of each other) serum cytokine and MRS showed correlations between Lac/NAA and serum IL-1β and IL-10 (all p < 0.01). The pro/anti-inflammatory ratios IL-1β/IL-10, IL-6/IL-10, IL-4/IL-10 and IL-8/IL-10 were similar in NT and HT groups until 36 h (24 h for IL-6/IL-10); after this, 36 h pro/anti-inflammatory cytokine ratios in the serum were higher in HT compared to NT (p < 0.05), indicating a pro-inflammatory cytokine surge after rewarming in the HT group. In the CSF at 48 h, IL-8 was lower in the HT group (p < 0.05). At 48 h, CSF TNF-α correlated with Lac/NAA (p = 0.02) and CSF IL-8 correlated with white matter TUNEL positive cell death (p = 0.04). CONCLUSIONS: Following cerebral HI, there was a systemic pro-inflammatory surge after rewarming in the HT group, which is counterintuitive to the putative neuroprotective effects of HT. While serum cytokines were variable, elevations in CSF inflammatory cytokines at 48 h were associated with MRS Lac/NAA and white matter cell death.

Type: Article
Title: Systemic pro-inflammatory cytokine status following therapeutic hypothermia in a piglet hypoxia-ischemia model.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12974-017-0821-x
Publisher version: http://dx.doi.org/10.1186/s12974-017-0821-x
Language: English
Additional information: © The Author(s). 2017. This 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.
Keywords: Biomarkers, Birth asphyxia, Cytokines, Magnetic resonance spectroscopy, Neuroprotection, Therapeutic hypothermia
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Neonatology
URI: https://discovery.ucl.ac.uk/id/eprint/1544768
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