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Leptin and fractalkine: novel subcutaneous cytokines in burn injury

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Title: Leptin and fractalkine: novel subcutaneous cytokines in burn injury
Authors: Friston, D
Junttila, S
Borges Paes Lemes, J
Laycock, H
Torres-Perez, J
Want, E
Gyenesei, A
Nagy, I
Item Type: Journal Article
Abstract: Burn injury is a pathology underpinned by progressive and aberrant inflammation. It is a major clinical challenge to survival and quality of life. While burn injury’s complex local and disseminating pathological processes ultimately stem from local tissue damage, to date relatively few studies have attempted to characterise the local inflammatory mediator profile. Here, cytokine content and associated transcriptional changes were measured in rat skin for three hours immediately following induction of a scald-type (60oC, 2 minutes) burn injury model. Leptin (p = 0.0002) and fractalkine (p = 0.0478) concentrations were significantly elevated post-burn above pre-burn and control site values, coinciding with the development of burn site oedema and differential expression of leptin mRNA (p = 0.0004). Further, gene sequencing enrichment analysis indicated cytokine-cytokine receptor interaction (p = 1.45x10-6). Subsequent behavioural studies demonstrated that, following subcutaneous injection into the dorsum of the paw, both leptin and fractalkine induced mechanical allodynia, heat hyperalgesia and the recruitment of macrophages. This is the first report of leptin’s elevation specifically at the burn site and the first report of fractalkine’s elevation in any tissue post-burn which, together with the functional findings, calls for exploration of the influence of these cytokines on pain, inflammation and burn wound progression. Additionally targeting these signalling molecules represents a therapeutic potential as early formative mediators of these pathological processes.
Issue Date: Apr-2020
Date of Acceptance: 24-Feb-2020
URI: http://hdl.handle.net/10044/1/72892
DOI: 10.1242/dmm.042713
ISSN: 1754-8403
Publisher: Company of Biologists
Journal / Book Title: Disease Models and Mechanisms
Volume: 13
Issue: 4
Copyright Statement: © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Sponsor/Funder: British Journal of Anaesthesia
NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research)
Wellcome Trust
Chelsea & Westminster Health Charity
Wellcome Trust
Funder's Grant Number: BJA/RCoA Grants
NC/K500409/1
102759/Z/13/Z
Capacity Building Project
102759/Z/13/Z
Keywords: Luminex
Microdialysis
RNAseq
Skin
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Article Number: ARTN dmm042713
Online Publication Date: 2020-04-29
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine