Mediators released during human anaphylaxis.

A range of mediators are generated during anaphylaxis, with redundancy of effects, multiple overlapping pathways, and involvement of several cell types. Key steps in the reaction occur at the site of initial contact, and mediators may not be detectable systemically. Furthermore, the potencies of various mediators vary enormously, and clinical effects may occur below our level of detection. We also do not know what converts (amplifies) a local reaction into systemic anaphylaxis. Murine models have identified several novel mediators that may propagate and/or regulate this process and also indicate that circulating neutrophils may play an important role in reaction amplification. Differential expression of various genes within specific intracellular signalling pathways of mediator release may further explain the varying severities of anaphylactic reactions. As our knowledge of the mechanisms of activation, key mediators, and the regulation of mediator release improves, new treatments for prevention and acute management may emerge.