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Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers

Buters, TP; Hameeteman, P; Jansen, IME; van Hindevoort, FC; Ten Voorde, W; Grievink, HW; Schoonakker, M; ... Moerland, M; + view all (2021) Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers. Clinical Pharmacology & Therapeutics 10.1002/cpt.2516. Green open access

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Abstract

The intradermal lipopolysaccharide (LPS) challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs. Twenty-four healthy male volunteers received a two-and-a-half-day twice daily (b.i.d.) pretreatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two-and-a-half-day b.i.d. pretreatment with oral prednisolone at 0.25 mg/kg body weight per administration. Participants received one injection regimen of either 0, 2, or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% sodium chloride solution). The LPS response was evaluated by noninvasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate. Both corticosteroids significantly suppressed the clinical inflammatory response (erythema P = 0.0001 for clobetasol and P = 0.0016 for prednisolone; heat P = 0.0245 for clobetasol, perfusion P < 0.0001 for clobetasol and P = 0.0036 for prednisolone). Clobetasol also significantly reduced the number of monocytes subsets, dendritic cells, natural killer cells, and T cells in blister exudate. A similar effect was observed for prednisolone. No relevant corticosteroid effects were observed on the cytokine response to LPS. We successfully demonstrated that the anti-inflammatory effects of corticosteroids can be detected using our intradermal LPS challenge model, validating it for evaluation of future investigational drugs, as an initial assessment of the anti-inflammatory effects of such compounds in a minimally invasive manner.

Type: Article
Title: Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cpt.2516
Publisher version: https://doi.org/10.1002/cpt.2516
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. See: http://creativecommons.org/licenses/by-nc-nd/4.0/
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/10142103
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