Related Experiment Videos
A lethal role of platelet activating factor in anaphylactic shock in mice
Z Terashita1, Y Imura, A Shino
1Central Research Division, Takeda Chemical Industries Ltd., Osaka, Japan.
Abstract:
The lethal role of platelet activating factor (PAF) in anaphylactic shock was examined in mice, using the specific PAF antagonist, CV-3988. CV-3988 (0.3-3 mg/kg i.v.), given 5 min before PAF, protected mice from death (ED50, 0.9 mg/kg). CV-3988 (3 mg/kg i.v.), given 1 min after PAF was injected, was also effective, but no so effective when given 5 min later. Dexamethasone (2 mg/kg i.v. 3 hr before the PAF-injection), naloxone (1 and 10 mg/kg i.v. 5 min before), FPL-55712 (10 mg/kg i.v. 5 min before) and BW-755c (300 mg/kg p.o. 1 hr before) also improved the survival rate, but aspirin (100 mg/kg p.o. 1 hr before) did not. In anaphylactic shock, CV-3988 (0.3-3 mg/kg i.v.), given 5 min before and 5 min after rechallenge with antigen protected the sensitized mice from death (ED50, 1.2 and 0.48 mg/kg, respectively). Dexamethasone and naloxone protected mice from anaphylactic shock, but BW-755c and FPL-55712 had no protective effects. In contrast to CV-3988, dexamethasone and naloxone were ineffective when given 5 min after the rechallenge. Congestion of the lung, kidney and heart and infiltration of neutrophils in the lung were marked in mice with PAF-induced and anaphylactic shock. The related histology showed an improvement with CV-3988. These results strongly suggest that PAF may play a lethal role in anaphylactic shock and that CV-3988 may be an effective preventing agent.
Insights
Platelet activating factor (PAF) plays a lethal role in anaphylactic shock. The PAF antagonist CV-3988 effectively protected mice from death when administered before or shortly after PAF exposure.
Area of Science:
- Immunology
- Pharmacology
- Pathophysiology
Background:
- Anaphylactic shock is a severe, life-threatening allergic reaction.
- Platelet-activating factor (PAF) is implicated in the pathophysiology of anaphylaxis.
- Understanding the role of PAF and identifying effective antagonists is crucial for treatment.
Purpose of the Study:
- To investigate the lethal role of platelet-activating factor (PAF) in anaphylactic shock.
- To evaluate the efficacy of the specific PAF antagonist, CV-3988, in preventing mortality.
- To compare the protective effects of CV-3988 with other agents like dexamethasone and naloxone.
Main Methods:
- Studies were conducted in mice models of PAF-induced shock and active anaphylaxis.
- The specific PAF antagonist CV-3988 was administered intravenously at various time points before and after PAF injection or antigen rechallenge.
- Survival rates were assessed, and histological examination of organs (lung, kidney, heart) was performed.
Main Results:
- CV-3988 demonstrated significant protection against PAF-induced death, with dose-dependent efficacy.
- Administration of CV-3988 shortly after PAF or antigen challenge improved survival rates.
- Histological analysis revealed reduced organ congestion and neutrophil infiltration in mice treated with CV-3988.
Conclusions:
- Platelet-activating factor (PAF) plays a critical lethal role in anaphylactic shock.
- The PAF antagonist CV-3988 is a highly effective agent for preventing mortality in anaphylaxis.
- CV-3988 shows promise as a therapeutic strategy for managing anaphylactic shock.