The Novel Role of Platelet-Activating Factor in Protecting Mice against Lipopolysaccharide-Induced Endotoxic Shock

Abstract

BackgroundPlatelet-activating factor (PAF) has been long believed to be associated with many pathophysiological processes during septic shock. Here we present novel activities for PAF in protecting mice against LPS-mediated endotoxic shock.Principal Findings In vivo PAF treatment immediately after LPS challenge markedly improved the survival rate against mortality from endotoxic shock. Administration of PAF prominently attenuated LPS-induced organ injury, including profound hypotension, excessive polymorphonuclear neutrophil infiltration, and severe multiple organ failure. In addition, PAF treatment protects against LPS-induced lymphocytes apoptosis. These protective effects of PAF was correlated with significantly decreases in the production of the inflammatory mediators such as TNF-α, IL-1β, IL-12, and IFN-γ, while increasing production of the anti-inflammatory cytokine IL-10 in vivo and in vitro.ConclusionsTaken together, these results suggest that PAF may protect mice against endotoxic shock via a complex mechanism involving modulation of inflammatory and anti-inflammatory mediators.

PAFR activation of NF-κB p65 or p105 precursor dictates pro- and anti-inflammatory responses during TLR activation in murine macrophages

“…In summary, our results show that PAF reduces the generation of pro-inflammatory cytokines and PGE 2 and increases the generation of anti-inflammatory IL-10 in macrophages stimulated with LPS or Pam3cys. Similar results were described by Jeong et al 27. in LPS-stimulated murine peritoneal macrophages where PAF was shown to potentiate IL-10 production and inhibit IL-12, IL-6, and TNF-α.…”

Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-α and IL-1β release and augmentation of IL-10 production

“…Recently, some researchers observed the effects of some immunomodulators on LPS-induced lethality, and found that these agents such as platelet-activating factor and glycine not only suppress TNF-α release but also augment IL-10 production induced by LPS and increase the survival rate of endotoxemic mice [23,24]. In this respect, we demonstrated for the first time that Pae could serve as an immunomodulator, and simultaneously regulate pro-inflammatory and anti-inflammatory mediator production during endotoxemia.…”

The Agonists of Formyl Peptide Receptors Prevent Development of Severe Sepsis after Microbial Infection

“…In this paper, we demonstrated that the administration of FPR family agonist WKYMVm after the induction of sepsis by CLP effectively prevented CLP-induced lethality in mice via multiple therapeutic pathways: 1) bactericidal activity that is partly mediated by IFN-g; 2) an anti-inflammatory effect via the downregulation of proinflammatory mediators, which is partly mediated by IL-17; and 3) an antiapoptotic effect on immune cells. Recently, Park and colleagues (40) demonstrated that a classical chemoattractant, platelet-activating factor, shows protective activity against LPSinduced endotoxic shock in an experimental animal model. On the basis of all these findings, we suggest that the functional role of classical chemoattractants and their receptors should be reconsidered as important target molecules for the development of therapeutic agents against infectious diseases.…”