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

Thomas P. Buters, Pieter W. Hameeteman, Iris M.E. Jansen, Floris C. van Hindevoort, Wouter ten Voorde, Edwin Florencia, Michelle Osse, Marieke L. de Kam, Hendrika W. Grievink, Mascha Schoonakker, Amit A. Patel, Simon Yona, Derek W. Gilroy, Erik Lubberts, Jeffrey Damman, Gary Feiss, Robert Rissmann, Manon A.A. Jansen, Jacobus Burggraaf, Matthijs Moerland*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 5 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.

Original languageAmerican English
Pages (from-to)680-690
Number of pages11
JournalBritish Journal of Clinical Pharmacology
Volume88
Issue number2
DOIs
StatePublished - Feb 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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