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.
Highlights
Sepsis is a serious and complex clinical syndrome caused by an overly active host response to infection. sepsis develops in 750,000 people annually, with more than 210,000 cases resulting in death in the United States alone[1]
Taken together, these results suggest that Platelet-activating factor (PAF) may protect mice against endotoxic shock via a complex mechanism involving modulation of inflammatory and anti-inflammatory mediators
The mortality of endotoxemic mice that received BN52021 were slightly delayed compared to those treated with vehicle alone, treatment with the PAF receptor (PAF-R) antagonist blocked the protective effects of PAF against LPS-induced lethality (Figure 1B)
Summary
Sepsis is a serious and complex clinical syndrome caused by an overly active host response to infection. sepsis develops in 750,000 people annually, with more than 210,000 cases resulting in death in the United States alone[1]. If the infection is not controlled and spreads beyond the local site, the systemic inflammatory response becomes hyperactive. This pervasive immune response often results in such detrimental complications as multiple organ failure, profound hypotension, and immune paralysis, all of which contribute to the high mortality observed in severe sepsis. Lipopolysaccharide (LPS) is responsible for initiating this process by inducing the uncontrolled release of proinflammatory mediators from immune cells, monocytes and macrophages. Major proinflammatory cytokines produced during an infection, including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, interferon (IFN-c), and IL-12, play a prominent roles in defective activation of the host immune response and sepsisinduced tissue injury [2,3,4,5]. We present novel activities for PAF in protecting mice against LPS-mediated endotoxic shock
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