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© Fabrice Chrétien with Ultrapole, colorized by Jean-Marc Panaud
Cellule souche (en jaune) de muscle squelettique partiellement recouverte par la membrane basale, migrant sur une fibre musculaire (en bleu).
Publication : Scientific reports

Reducing hypoxia and inflammation during invasive pulmonary aspergillosis by targeting the Interleukin-1 receptor

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Scientific reports - 24 May 2016

Gresnigt MS, Rekiki A, Rasid O, Savers A, Jouvion G, Dannaoui E, Parlato M, Fitting C, Brock M, Cavaillon JM, van de Veerdonk FL, Ibrahim-Granet O

Link to Pubmed [PMID] – 27215684

Sci Rep 2016;6:26490

Hypoxia as a result of pulmonary tissue damage due to unresolved inflammation during invasive pulmonary aspergillosis (IPA) is associated with a poor outcome. Aspergillus fumigatus can exploit the hypoxic microenvironment in the lung, but the inflammatory response required for fungal clearance can become severely disregulated as a result of hypoxia. Since severe inflammation can be detrimental to the host, we investigated whether targeting the interleukin IL-1 pathway could reduce inflammation and tissue hypoxia, improving the outcome of IPA. The interplay between hypoxia and inflammation was investigated by in vivo imaging of hypoxia and measurement of cytokines in the lungs in a model of corticosteroid immunocompromised and in Cxcr2 deficient mice. Severe hypoxia was observed following Aspergillus infection in both models and correlated with development of pulmonary inflammation and expression of hypoxia specific transcripts. Treatment with IL-1 receptor antagonist reduced hypoxia and slightly, but significantly reduced mortality in immunosuppressed mice, but was unable to reduce hypoxia in Cxcr2(-/-) mice. Our data provides evidence that the inflammatory response during invasive pulmonary aspergillosis, and in particular the IL-1 axis, drives the development of hypoxia. Targeting the inflammatory IL-1 response could be used as a potential immunomodulatory therapy to improve the outcome of aspergillosis.

http://www.ncbi.nlm.nih.gov/pubmed/27215684