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Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers

Buters, TP; Hameeteman, PW; Jansen, IME; van Hindevoort, FC; Ten Voorde, W; Florencia, E; Osse, M; ... Moerland, M; + view all (2021) Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers. British Journal of Clinical Pharmacology 10.1111/bcp.14999. (In press). Green open access

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Abstract

Aims: Whereas intravenous administration of Toll-like receptor 4 ligand lipopolysaccharide (LPS) to human volunteers is frequently used in clinical pharmacology studies, systemic use of LPS has practical limitations. We aimed to characterize the intradermal LPS response in healthy volunteers, and as such qualify the method as local inflammation model for clinical pharmacology studies. Methods: Eighteen healthy male volunteers received 2 or 4 intradermal 10 ng LPS injections and 1 saline injection on the forearms. The LPS response was evaluated by noninvasive (perfusion, skin temperature and erythema) and invasive assessments (cellular and cytokine responses) in skin biopsy and blister exudate. Results: LPS elicited a visible response and returned to baseline at 48 hours. Erythema, perfusion and temperature were statistically significant (P < .0001) over a 24-hour time course compared to saline. The protein response was dominated by an acute interleukin (IL)-6, IL-8 and tumour necrosis factor response followed by IL-1β, IL-10 and interferon-γ. The cellular response consisted of an acute neutrophil influx followed by different monocyte subsets and dendritic cells. Discussion: Intradermal LPS administration in humans causes an acute, localized and transient inflammatory reaction that is well-tolerated by healthy volunteers. This may be a valuable inflammation model for evaluating the pharmacological activity of anti-inflammatory investigational compounds in proof of pharmacology studies.

Type: Article
Title: Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/bcp.14999
Publisher version: http://dx.doi.org/10.1111/bcp.14999
Language: English
Additional information: © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: drug development, endotoxin, healthy volunteers, inflammatory model, intradermal LPS, B-CELLS, SKIN, NEUTROPHILS, ACTIVATION, MECHANISMS, TOLERANCE, ENDOTOXIN, ROLES, STATE
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 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
URI: https://discovery.ucl.ac.uk/id/eprint/10134487
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