Exudate suction blister: a novel in vivo model of acute infllammation and resolution in humans. (CAM1P.145)

Abstract Resolution of acute inflammation is an active process and its dysregulation may contribute to chronic inflammatory disorders. While animal models have been used to study resolution their appropriateness has been questioned. We describe a novel model of resolving inflammation in humans triggered by intradermal injection of UV killed E. coli into the forearm of healthy volunteers (n=30). Inflammatory exudate was drawn into a skin blister induced by negative pressure applied over the injection site. Blister cells were analyzed by flow cytometry while the cell free exudates were assayed for cytokines. To study the different phases of inflammation, blisters were raised at multiple time points up to day 14 post-injection. Vascular response was monitored by laser doppler. Onset (8hr) was characterised by peak erythema and neutrophilia (HLA-DR-/CD16++). By 24hr, neutrophil numbers had fallen by 80% while CD14+ monocytes and CD1c+ dendritic cell numbers increased, indicating resolution. At 48hr blood flow declined along with mononuclear cell numbers. Lymphocytes (CD4+, CD8+ and CD56+ cells) dominated the site at day 3 and persisted up to day 14. Levels of TNF-α, IL-8 and IL-1β were maximal at 8hr, IFN-γ at 24hr. This safe and reproducible model allows, for the first time, exploration of cells and soluble mediators in parallel with the clinical signs of resolution in humans. Potential applications include testing the efficacy of novel anti-inflammatory and pro-resolving drugs.