| Author | Gomes, Rachel N. | |
| Author | Bozza, Fernando A. | |
| Author | Amâncio, Rodrigo T. | |
| Author | Japiassú, André M. | |
| Author | Vianna, Rosa C. S. | |
| Author | Larangeira, Andréa P. | |
| Author | Gouvêa, Juliana M. | |
| Author | Bastos, Marcela S. | |
| Author | Zimmerman, Guy A. | |
| Author | Stafforini, Diana M. | |
| Author | Prescott, Stephen M. | |
| Author | Bozza, Patrícia T. | |
| Author | Faria Neto, Hugo Caire C. | |
| Access date | 2020-01-07T13:50:45Z | |
| Available date | 2020-01-07T13:50:45Z | |
| Document date | 2006 | |
| Citation | GOMES, Rachel N. et al. Exogenous platelet-activating factor acetylhydrolase reduces mortality in mice with systemic inflammatory response syndrome and sepsis. Shock. Injury, Inflammation and Sepsis, v. 26, n. 1, p. 41-49, July 2006. | pt_BR |
| ISSN | 1073-2322 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/39027 | |
| Language | eng | pt_BR |
| Publisher | Lippincott, Williams & Wilkins | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Sepse | pt_BR |
| Subject in Portuguese | Citocinas | pt_BR |
| Subject in Portuguese | Fator de ativação plaquetária recombinante | pt_BR |
| Title | Exogenous platelet-activating factor acetylhydrolase reduces mortality in mice with systemic inflammatory response syndrome and sepsis | en_US |
| Type | Article | |
| DOI | 10.1097/01.shk.0000209562.00070.1a | pt_BR |
| Abstract | Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the mortality of patients with sepsis and in those with systemic inflammatory response syndrome. Strategies to block inflammatory mediators, often with complicated outcomes, are currently being investigated as new adjuvant therapies for sepsis. Here, we determined if administration of recombinant platelet-activating factor (rPAF)-acetylhydrolase (rPAF-AH), an enzyme that inactivates PAF and PAF-like lipids, protects mice from inflammatory injury and death after administration of lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). Administration of rPAF-AH increased plasma PAF-AH activity and reduced mortality in both models. Treatment with rPAF-AH increased peritoneal fluid levels of monocyte chemoattractant protein 1/CCL-2 and decreased interleukin 6 and migration inhibitory factor levels after LPS administration or CLP. Administration of a broad-spectrum antibiotic together with rPAF-AH was more protective than single treatment with either of these agents. The combined treatment was associated with reduced interleukin 6 levels in mice subjected to CLP. We observed acute decreases in plasma PAF-AH activity in mice subjected to CLP or challenged with LPS and in human patients with sepsis. We conclude that alterations in the endogenous PAF-AH contribute to the pathophysiology of sepsis and that administration of exogenous rPAF-AH reduces inflammatory injury and mortality in models relevant to the clinical syndrome. Variations in endogenous PAF-AH activity may potentially account for variable responses to exogenous rPAF-AH in previous clinical trials. Serial measurements of plasma PAF-AH activity in murine models demonstrate dynamic regulation of the endogenous enzyme, potentially explaining the variations in human subjects. | en |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Hospital Universitário Clementino Fraga Filho. Centro de Tratamento Intensivo. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Hospital Universitário Clementino Fraga Filho. Centro de Tratamento Intensivo. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Hospital Universitário Clementino Fraga Filho. Centro de Tratamento Intensivo. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Laboratório de Tecnologia Bacteriana. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | University of Utah. Program in Human Molecular Biology and Genetics. Salt Lake City, Utah, USA. | pt_BR |
| Affilliation | University of Utah. Huntsman Cancer Institute. Salt Lake City, Utah, USA. | pt_BR |
| Affilliation | University of Utah. Huntsman Cancer Institute. Salt Lake City, Utah, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Sepsis | en |
| Subject | PAF | en |
| Subject | PAF-AH | en |
| Subject | Cytokines | en |
| Subject | SIRS | en |
| e-ISSN | 1540-0514 | pt_BR |
| Embargo date | 2025-01-01 | |
