Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

This study examined the establishment of neutrophilic inflammation in humans. We tested the hypotheses that neutrophil recruitment was associated with local CXCL8 production and that neutrophils themselves might contribute to the regulation of the size of the inflammatory response. Humans were challenged i.d. with endotoxin. Biopsies of these sites were examined for cytokine production and leukocyte recruitment by qPCR and IHC. Additional in vitro models of inflammation examined the ability of neutrophils to produce and sequester cytokines relevant to neutrophilic inflammation. i.d. challenge with 15 ng of a TLR4-selective endotoxin caused a local inflammatory response, in which 1% of the total biopsy area stained positive for neutrophils at 6 h, correlating with 100-fold up-regulation in local CXCL8 mRNA generation. Neutrophils themselves were the major source of the early cytokine IL-1β. In vitro, neutrophils mediated CXCL8 but not IL-1β clearance (>90% clearance of ≤2 nM CXCL8 over 24 h). CXCL8 clearance was at least partially receptor-dependent and modified by inflammatory context, preserved in models of viral infection but reduced in models of bacterial infection. In conclusion, in a human inflammatory model, neutrophils are rapidly recruited and may regulate the size and outcome of the inflammatory response through the uptake and release of cytokines and chemokines in patterns dependent on the underlying inflammatory stimulus.

Original publication

DOI

10.1189/jlb.0512250

Type

Journal article

Journal

Journal of leukocyte biology

Publication Date

01/2013

Volume

93

Pages

7 - 19

Addresses

Department of Infection and Immunity, Faculty of Medicine, Dentistry and Health, University of Sheffield, Beech Hill Rd., Sheffield, UK.

Keywords

Neutrophils, Skin, Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Mice, Inflammation, Chemokines, Interleukin-8, Interleukin-1, Endotoxins, Blotting, Western, Immunohistochemistry, Neutrophil Activation, Neutrophil Infiltration