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

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...

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Veröffentlicht in:British journal of clinical pharmacology 2022-02, Vol.88 (2), p.680-690
Hauptverfasser: Buters, Thomas P., Hameeteman, Pieter W., Jansen, Iris M. E., Hindevoort, Floris C., Voorde, Wouter, Florencia, Edwin, Osse, Michelle, Kam, Marieke L., Grievink, Hendrika W., Schoonakker, Mascha, Patel, Amit A., Yona, Simon, Gilroy, Derek W., Lubberts, Erik, Damman, Jeffrey, Feiss, Gary, Rissmann, Robert, Jansen, Manon A. A., Burggraaf, Jacobus, Moerland, Matthijs
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Sprache:eng
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Zusammenfassung: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 
ISSN:0306-5251
1365-2125
DOI:10.1111/bcp.14999