Involvement of Platelet-Activating Factor (PAF) in Septic Shock and Priming as Indicated by the Effect of Hetrazepinoic PAF Antagonists

Abstract

Pharmacological data obtained with hetrazepinoic platelet-activating factor (PAF) antagonists, such as apafant (WEB 2086) and bepafant (WEB 2170), indicate a role for PAF in septic shock and in the priming process. The effect of PAF antagonists in different models of shock states favors a role for PAF in endotoxin associated lethality, activation of inflammatory blood cells with release of mediators, cardiovascular failure and increased vascular permeability, and in the development of shock organs and organ failure~ The priming process (e~g., by endotoxin or tumor necrosis factor) towards an increased susceptibility towards minute amounts of PAF has to be taken into account when considering the pathophysiological significance of PAF under in vivo conditions and in septic shock.

Paricalcitol Effects on Activities and Metabolism of Platelet Activating Factor and on Inflammatory Cytokines in Hemodialysis Patients

“…Paricalcitol effectively inhibited in vitro PAF-induced platelet aggregation of both WRPs and rPRP with an IC 50 of 338.2 ± 58.1 nM and 1067.3 ± 132.0 nM, respectively. The inhibitory effect of paricalcitol was comparable to those of some of the most potent and specific PAF receptor antagonists (33-35). Also, thrombin-induced platelet aggregation of WRPs was inhibited by paricalcitol with an IC 50 of 675.4 ± 74.7 nM.…”

In Vitro and In Vivo Effects of Statins on Platelet-Activating Factor and Its Metabolism

“…We found for the first time that statins inhibit PAF-induced aggregation in a dose-dependent manner in both WRPs and hPRP. The IC 50 values of statins for PAF-induced platelet aggregation, compared with those of some of the most potent and specific PAF receptor antagonists (eg, WEB2170, BN52021, and Rupatadine; 20, 30, and 260 nmol/L, respectively) [41][42][43] showed that statins also exhibit a strong inhibitory effect against PAF activity.…”

COVID‐19, microthromboses, inflammation, and platelet activating factor

“…Many biological actions of PAF are similar to COVID‐19 disease manifestations. In particular, PAF is implicated in the development of sepsis 56 and the most recently reported Kawasaki‐like disease in children 57 . SARS‐CoV‐1 has the ability to induce production of compounds like oxidized‐phospholipid (OxPL), which then induce cytokine production and acute lung injury via Toll‐like receptor 4 (TLR4) 58 .…”