Article
Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration
Registro en:
CUNHA, Mariana G. A. Teixeira da; Bacterial Clearance Is Improved in Septic Mice by Platelet-Activating Factor-Acetylhydrolase (PAF-AH) Administration. Plos One, v.8, n.9, e74567. 7p, 2013.
1932-6203
10.1371/journal.pone.0074567
Autor
Cunha, Mariana G. A. Teixeira da
Gomes, Rachel N.
Roehrs, Nathassia
Bozza, Fernando A.
Prescott, Stephen M.
Stafforini, Diana
Zimmerman, Guy A.
Bozza, Patrícia T.
Faria Neto, Hugo C. Castro
Resumen
Current evidence indicates that dysregulation of the host inflammatory response to infectious agents is central to the
mortality of patients with sepsis. Strategies to block inflammatory mediators such as PAF have been investigated as
adjuvant therapies for sepsis. PAF-AH, the enzyme responsible for PAF degradation, showed positive results in pre-clinical
studies and phase II clinical trials, but the results of a phase III study were disappointing. In this study, we investigated the
potential protective mechanism of PAF-AH in sepsis using the murine model of cecal ligation and puncture (CLP). Treatment
with rPAF-AH increased peritoneal fluid levels of the anti-inflammatory mediators MCP-1/CCL2 after CLP. The numbers of
bacteria (CFU) in the peritoneal cavity were decreased in the rPAF-AH-treated group, indicating more efficient bacterial
clearance after rPAF-AH treatment. Interestingly, we observed increased levels of nitric oxide (NO) after PAF-AH
administration, and rPAF-AH treatment did not decrease CFU numbers either in iNOS-deficient mice or in CCR2-deficient
mice. We concluded that administration of exogenous rPAF-AH reduced inflammatory injury, altered cytokine levels and
favored bacterial clearance with a clear impact on mortality through modulation of MCP-1/CCL2 and NO levels in a clinically
relevant sepsis model.