Anaphylaxis (P Lieberman, Section Editor)

Current Treatment Options in Allergy

, Volume 1, Issue 3, pp 232-246

Potential Therapeutic Strategies for Severe Anaphylaxis Targeting Platelet-Activating Factor and PAF Acetylhydrolase

  • Julia UptonAffiliated withClinical Immunology and Allergy, Department of Pediatrics, The Hospital for Sick ChildrenUniversity of Toronto Email author 
  • , Peter VadasAffiliated withDivision of Allergy and Clinical Immunology, St. Michael’s HospitalDepartment of Medicine, University of Toronto

Opinion statement

Characterization of mediators and mechanisms of anaphylaxis will allow for more specific and effective treatment with fewer side effects. Recent studies have shown that platelet-activating factor (PAF) is a pivotal mediator of the life-threatening manifestations of anaphylaxis. The putative role of PAF in human anaphylaxis is based on a large body of evidence in experimental and human anaphylaxis. In animal models of anaphylaxis, intravenous administration of PAF reproduces the severe physiologic derangements of anaphylaxis. PAF receptor knock-out mice are resistant to experimental anaphylaxis. Data from human anaphylaxis show that levels of PAF increase proportionately with the severity of anaphylaxis, whereas a deficiency in the enzyme that inactivates PAF predisposes to severe or fatal anaphylaxis. Many of the biologic effects of PAF appear to be transduced by nitric oxide production. PAF receptor antagonists protect against the lethal effects of exogenous PAF, but, importantly, also protect against experimental anaphylaxis following allergen challenge. Mice treated with an enzyme that inactivates PAF are similarly resistant to anaphylaxis. Some clinically available medications for anaphylaxis act at different points of the PAF pathway. Epinephrine, the first-line treatment for anaphylaxis, appears to act in part by phosphorylation and inactivation of the PAF receptor, whereas methylene blue, which reduces the actions of nitric oxide, can reverse severe anaphylaxis that is refractory to conventional treatment. Taken together, these studies have shown that therapies targeting the PAF pathway might hold the potential for more specific and effective treatments for this potentially life-threatening condition.


Platelet-activating factor Platelet-activating factor acetylhydrolase Platelet-activating factor receptor antagonists Anaphylaxis Methylene blue Ginkgolide