Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection

Alves Filho, J. C. et al. (2010) Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nature Medicine, 16(6), pp. 708-712. (doi: 10.1038/nm.2156)

Full text not currently available from Enlighten.

Publisher's URL:


Sepsis is a systemic inflammatory condition following bacterial infection with a high mortality rate and limited therapeutic options(1,2). Here we show that interleukin-33 (IL-33) reduces mortality in mice with experimental sepsis from cecal ligation and puncture (CLP). IL-33-treated mice developed increased neutrophil influx into the peritoneal cavity and more efficient bacterial clearance than untreated mice. IL-33 reduced the systemic but not the local proinflammatory response, and it did not induce a T helper type 1 (T(H)1) to T(H)2 shift. The chemokine receptor CXCR2 is crucial for recruitment of neutrophils from the circulation to the site of infection(3). Activation of Toll-like receptors (TLRs) in neutrophils downregulates CXCR2 expression and impairs neutrophil migration(4). We show here that IL-33 prevents the downregulation of CXCR2 and inhibition of chemotaxis induced by the activation of TLR4 in mouse and human neutrophils. Furthermore, we show that IL-33 reverses the TLR4-induced reduction of CXCR2 expression in neutrophils via the inhibition of expression of G protein coupled receptor kinase-2 (GRK2), a serine-threonine protein kinase that induces internalization of chemokine receptors(5,6). Finally, we find that individuals who did not recover from sepsis had significantly more soluble ST2 (sST2, the decoy receptor of IL-33) than those who did recover. Together, our results indicate a previously undescribed mechanism of action of IL-33 and suggest a therapeutic potential of IL-33 in sepsis

Item Type:Articles
Keywords:activation, allergy, biology, blood, care, cell biology, chemokine, cytokine, decoy, expression, human, human neutrophils, IL-33, immune-responses, immunity, impairs, individuals, infection, inhibition, mast-cells, mechanism, mice, migration, mortality, mouse, polymicrobial sepsis, protein, protein-kinase, receptor, receptor accessory protein, recruitment, reduction, shock, site, ST2, TH2 cells, toll like receptors, toll-like receptors
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Xu, Dr Damo and Sonego, Ms Fabiane and Alves-Filho, Dr Jose
Authors: Alves Filho, J. C., Sonego, F., Souto, F. O., Freitas, A., Verri, W. A., Auxiliadora-Martins, M., Basile-Filho, A., McKenzie, A. N., Xu, D., Cunha, F. Q., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Nature Medicine
Publisher:Nature Publishing Group
ISSN (Online):1546-170X
Published Online:16 May 2010
Related URLs:

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198Infection Immunity and Inflammation Medicine