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Immunomodulatory effects and protection of moxifloxacin in sepsis

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Summary:Sepsis is a complex syndrome that results from a harmful systemic inflammatory response to infection. It is the leading cause of death in Intensive Care Units, excluding neurotrauma, and the third most important cause of death in the hospital. However, it remains poorly understood, and in fact, in the past decades there have been no substantial advances in the treatment of this condition. As TNF-α and IL-1β are two important initial mediators of sepsis, immunomodulatory agents may be useful in the treatment of sepsis. Here we show that moxifloxacin, a fourth-generation fluoroquinolone with a broad antibacterial spectrum, has immunodulatory effects both in an in vitro assay and in a mice model of sepsis. Moxifloxacin protects against severe sepsis in mice, reducing the levels of cytokines and organ lesion markers. Moreover, our findings demonstrate that its actions are not due to its antibacterial effect and that its interaction with topoisomerase II or IV may not be relevant for the observed effects. The molecular mechanisms that explain its immunomodulatory effects remain unknown, and are certainly an interesting topic for future studies.
Main Authors:Velho, Tiago Rodrigues
Subject:IL-1β TNF-α Sepsis Moxifloxacin
Year:2014
Country:Portugal
Document type:master thesis
Access type:restricted access
Associated institution:Universidade de Lisboa
Language:English
Origin:Repositório da Universidade de Lisboa
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author Velho, Tiago Rodrigues
author_facet Velho, Tiago Rodrigues
author_role author
contributor_name_str_mv Moita, Luís Ferreira
Repositório Científico de Acesso Aberto da ULisboa
country_str PT
creators_json_txt [{\"Person.name\":\"Velho, Tiago Rodrigues\"}]
datacite.contributors.contributor.contributorName.fl_str_mv Moita, Luís Ferreira
Repositório Científico de Acesso Aberto da ULisboa
datacite.creators.creator.creatorName.fl_str_mv Velho, Tiago Rodrigues
datacite.date.Accepted.fl_str_mv 2014-01-01T00:00:00Z
datacite.date.available.fl_str_mv 2016-07-26T11:22:18Z
datacite.date.embargoed.fl_str_mv 2016-07-26T11:22:18Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_16ec
datacite.subjects.subject.fl_str_mv IL-1β
TNF-α
Sepsis
Moxifloxacin
datacite.titles.title.fl_str_mv Immunomodulatory effects and protection of moxifloxacin in sepsis
dc.contributor.none.fl_str_mv Moita, Luís Ferreira
Repositório Científico de Acesso Aberto da ULisboa
dc.creator.none.fl_str_mv Velho, Tiago Rodrigues
dc.date.Accepted.fl_str_mv 2014-01-01T00:00:00Z
dc.date.available.fl_str_mv 2016-07-26T11:22:18Z
dc.date.embargoed.fl_str_mv 2016-07-26T11:22:18Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10451/24458
dc.language.none.fl_str_mv eng
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_16ec
dc.subject.none.fl_str_mv IL-1β
TNF-α
Sepsis
Moxifloxacin
dc.title.fl_str_mv Immunomodulatory effects and protection of moxifloxacin in sepsis
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_bdcc
description Sepsis is a complex syndrome that results from a harmful systemic inflammatory response to infection. It is the leading cause of death in Intensive Care Units, excluding neurotrauma, and the third most important cause of death in the hospital. However, it remains poorly understood, and in fact, in the past decades there have been no substantial advances in the treatment of this condition. As TNF-α and IL-1β are two important initial mediators of sepsis, immunomodulatory agents may be useful in the treatment of sepsis. Here we show that moxifloxacin, a fourth-generation fluoroquinolone with a broad antibacterial spectrum, has immunodulatory effects both in an in vitro assay and in a mice model of sepsis. Moxifloxacin protects against severe sepsis in mice, reducing the levels of cytokines and organ lesion markers. Moreover, our findings demonstrate that its actions are not due to its antibacterial effect and that its interaction with topoisomerase II or IV may not be relevant for the observed effects. The molecular mechanisms that explain its immunomodulatory effects remain unknown, and are certainly an interesting topic for future studies.
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eu_rights_str_mv restrictedAccess
format masterThesis
fulltext.url.fl_str_mv https://repositorio.ulisboa.pt/bitstreams/58bf0f32-68aa-4e33-911c-7630b63890c8/download
id ul_6b065e1d3274d071db3183bffaefcfbd
identifier.url.fl_str_mv http://hdl.handle.net/10451/24458
inst_facet_str urn:organizationAcronym:ul{{{_:::_}}}Universidade de Lisboa
instacron_str ul
institution Universidade de Lisboa
instname_str Universidade de Lisboa
language eng
network_acronym_str ul
network_name_str Repositório da Universidade de Lisboa
oai_identifier_str oai:repositorio.ulisboa.pt:10451/24458
organization_str_mv urn:organizationAcronym:ul
person_str_mv Velho, Tiago Rodrigues
publishDate 2014
repo_facet_str urn:repositoryAcronym:ul{{{_:::_}}}Repositório da Universidade de Lisboa
reponame_str Repositório da Universidade de Lisboa
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spelling engpt_PTSepsis is a complex syndrome that results from a harmful systemic inflammatory response to infection. It is the leading cause of death in Intensive Care Units, excluding neurotrauma, and the third most important cause of death in the hospital. However, it remains poorly understood, and in fact, in the past decades there have been no substantial advances in the treatment of this condition. As TNF-α and IL-1β are two important initial mediators of sepsis, immunomodulatory agents may be useful in the treatment of sepsis. Here we show that moxifloxacin, a fourth-generation fluoroquinolone with a broad antibacterial spectrum, has immunodulatory effects both in an in vitro assay and in a mice model of sepsis. Moxifloxacin protects against severe sepsis in mice, reducing the levels of cytokines and organ lesion markers. Moreover, our findings demonstrate that its actions are not due to its antibacterial effect and that its interaction with topoisomerase II or IV may not be relevant for the observed effects. The molecular mechanisms that explain its immunomodulatory effects remain unknown, and are certainly an interesting topic for future studies.application/pdfpt_PTImmunomodulatory effects and protection of moxifloxacin in sepsisVelho, Tiago RodriguesMoita, Luís FerreiraHostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@ulisboa.ptrepositorio@ulisboa.ptURNurn:tid:2014702332016-07-26T11:22:18Z20142014-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/24458http://purl.org/coar/access_right/c_16ecrestricted accessIL-1βTNF-αSepsisMoxifloxacin1463129 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesishttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/58bf0f32-68aa-4e33-911c-7630b63890c8/download
spellingShingle Immunomodulatory effects and protection of moxifloxacin in sepsis
Velho, Tiago Rodrigues
IL-1β
TNF-α
Sepsis
Moxifloxacin
status SINGLETON
subject.fl_str_mv IL-1β
TNF-α
Sepsis
Moxifloxacin
title Immunomodulatory effects and protection of moxifloxacin in sepsis
title_full Immunomodulatory effects and protection of moxifloxacin in sepsis
title_fullStr Immunomodulatory effects and protection of moxifloxacin in sepsis
title_full_unstemmed Immunomodulatory effects and protection of moxifloxacin in sepsis
title_short Immunomodulatory effects and protection of moxifloxacin in sepsis
title_sort Immunomodulatory effects and protection of moxifloxacin in sepsis
topic IL-1β
TNF-α
Sepsis
Moxifloxacin
topic_facet IL-1β
TNF-α
Sepsis
Moxifloxacin
url http://hdl.handle.net/10451/24458
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