title: Novel translational model of resolving inflammation triggered by UV-killed E. coli.
abstract: Whilst numerous studies investigating the aetiology of inflammatory diseases have been performed in rodents, the applicability of these data to human pathophysiology is frequently debated. Regardless of the strengths and weaknesses of rodent models in biomedical research, there is a need to develop models of experimental inflammation in humans. Here, we describe a self-resolving acute inflammatory response triggered by the intradermal injection of UV-killed Escherichia coli into the forearm of healthy volunteers. Cells and exudates were harvested from onset to resolution by applying negative pressure over the inflamed site. Onset was characterized by high blood flow, neutrophilia and peak levels of pro-inflammatory cytokines, whilst resolution showed a decline in blood blow, reduction in neutrophils, increase in monocytes/macrophages and waning of classic pro-inflammatory cytokine levels. An anti-inflammatory effect, defined as suppression of onset phase events, was demonstrated by administering naproxen, a conventional non-steroidal anti-inflammatory drug. In summary, this model of resolving acute inflammation is minimally invasive, highly tractable and allows simultaneous investigation of the vascular response, cellular trafficking and chemical mediator profile of onset and resolution phases of acute inflammation in humans. It can serve as a translational platform to provide mechanistic insights and to test the clinical efficacy of novel anti-inflammatory and pro-resolving drugs, and also as a tool in patients to explore inherent defects in resolution pathways.
authors: Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, 5 University Street University College London London WC1E 6JF UK.
authors: Madhur P
authors: MP
authors: Motwani
authors: Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, 5 University Street University College London London WC1E 6JF UK.
authors: Julia D
authors: JD
authors: Flint
authors: Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, 5 University Street University College London London WC1E 6JF UK.
authors: Roel Ph
authors: RP
authors: De Maeyer
authors: Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, 5 University Street University College London London WC1E 6JF UK.
authors: James N
authors: JN
authors: Fullerton
authors: Microbial Diseases, Eastman Dental Institute, University College London London WC1X 8LD UK.
authors: Andrew M
authors: AM
authors: Smith
authors: Centre for Molecular Medicine, Division of Medicine, 5 University Street University College London London WC1E 6JF UK.
authors: Daniel Jb
authors: DJ
authors: Marks
authors: Centre for Clinical Pharmacology and Therapeutics, Division of Medicine, 5 University Street University College London London WC1E 6JF UK.
authors: Derek W
authors: DW
authors: Gilroy
keywords: human in vivo model; macrophage; neutrophil; resolution of inflammation; translational research