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Reference: Weehuizen, TAF, Lankelma, JM, de Jong, HK et al., (2016). Therapeutic administration of a monoclonal anti-Il-1β antibody protects against experimental melioidosis. Shock, 46 (5), 566-574.Citable link to this page:

 

Therapeutic administration of a monoclonal anti-Il-1β antibody protects against experimental melioidosis

Abstract: BACKGROUND:: Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a common cause of community-acquired sepsis in Southeast Asia and Northern Australia. The NLRP3-inflammasome and its downstream product interleukin-1 beta (IL-1β) have been proposed to play crucial roles in melioidosis. In this study we characterized the role of IL-1β more closely and we assessed its therapeutic potential. METHODS:: mRNA expression of inflammasome components was determined in isolated leukocytes of 32 healthy controls and 34 patients with sepsis caused by B. pseudomallei.Wild-type (WT), NLRP3-deficient (Nlrp3) and Asc mice were infected with B. pseudomallei. In additional experiments, infected WT mice were treated with an anti-IL-1β antibody. After 24, 48 and 72?hours (h) mice were sacrificed and organs were harvested. Furthermore, survival studies were performed. RESULTS:: Patients with melioidosis exhibited lower mRNA levels of caspase-1, NLRP3 and ASC. Bacterial dissemination and organ damage were increased in B. pseudomallei-infected Nlrp3 and Asc mice, together with a reduced pulmonary cell influx. Anti-IL-1β treatment of B. pseudomallei challenged mice resulted in strongly reduced bacterial counts, organ damage and pulmonary granulocyte influx together with reduced mortality. Postponement of anti-IL-1β treatment for 24?h post-infection still protected mice during melioidosis. CONCLUSION:: Expression of caspase-1, NLRP3 and ASC is altered in melioidosis patients. In mice, both NLRP3 and ASC contribute to the host defense against melioidosis. Anti-IL-1β treatment protects mice against B. pseudomallei infection and might be a novel treatment strategy in melioidosis.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:23 May 2016 Funder: Netherlands Organisationfor Health Research and Development   Funder: NetherlandsOrganization for Scientific Research   Notes:Copyright © 2016 by the Shock Society. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0

Bibliographic Details

Publisher: Lippincott, Williams & Wilkins

Publisher Website: http://www.lww.com/

Journal: Shocksee more from them

Publication Website: http://www.shockjournal.com/

Volume: 46

Issue: 5

Extent: 566-574

Issue Date: 23 May 2016

pages:566-574Identifiers

Doi: https://doi.org/10.1097/SHK.0000000000000625

Eissn: 1540-0514

Issn: 1073-2322

Uuid: 8326edab-4e8a-460b-8982-f39fed09c746

Urn: uri:8326edab-4e8a-460b-8982-f39fed09c746

Pubs-id: pubs:625184 Item Description

Type: journal-article;

Language: ENG

Version: Publisher's versionKeywords: anti-interleukin-1β Burkholderia pseudomallei melioidosis NLRP3 ASC sepsis

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Autor: Weehuizen, TAF - - - Lankelma, JM - - - de Jong, HK - - - de Boer, OJ - - - Roelofs, JJTH - - - Day, Nicholas - Oxford, MSD, NDM,

Fuente: https://ora.ox.ac.uk/objects/uuid:8326edab-4e8a-460b-8982-f39fed09c746



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