Critical evaluation of the key mediators causing life-threatening symptoms during human anaphylaxis.

Most pathophysiologically oriented anaphylaxis reviews list a plethora of mediators purportedly involved in symptom development during severe anaphylaxis. However, how many mediators are responsible for life-threatening anaphylaxis symptoms? In a recent review, we analysed available human data and determined that leukotrienes are unlikely to represent important direct mediators during anaphylaxis. Herein, we review the role of platelet-activating factor, another supposed mediator directly causing severe symptoms during mast cell activation. The conclusion drawn from many human studies is simple but not en vogue in the pharmaceutical and biotechnology industry, to the detriment of patients who die from mast cell activation during severe anaphylaxis, including acute asthma exacerbations.