Anaphylactic shock is an extreme allergic reaction which can be caused by a number of stimuli, including food, drugs and insect bites. It causes severe and rapid inflammation which can lead to breathing difficulties. If left untreated, the condition can be fatal.
PAF is a chemical released by immune cells such as mast cells and macrophages. During inflammation (such as in anaphylactic shock) these cells produce more PAF. Peter Vadas and colleagues found that the levels of PAF in the blood correlate with the severity of an anaphylactic reaction. Vadas et al graded anaphylactic shock reactions from Grade 1 to Grade 3, with 3 being the most severe reaction.
The study found lower levels of PAF in those having mild reactions, and significantly elevated levels of PAF in all Grade 3 subjects who were experiencing a severe anaphylactic reaction. Levels of PAF were also measured in the blood of healthy volunteers. Those with grade 1 anaphylaxis had blood PAF levels 2.5 times greater than normal. For severity grades 2 and 3, the figure was 5 and 10 times greater than normal, respectively. This demonstrates PAF to be a pivotal mediator of anaphylaxis, as its concentration in the blood increases proportional to the severity of the allergic reaction.
This raises the possibility of designing drug therapies which selectively block the actions of PAF, for use in the treatment of severe allergic reactions.
If the actions of PAF were blocked, platelet IgE would not be released, and inflammation could be reduced. Additionally, there is a possibility that anaphylactic reactions could be treated by preventing the actions of PAF. Vadas et al suggest that drugs which block PAF could be used as a ‘rescue’ therapy for patients in anaphylactic shock, or alternatively as a chronic treatment for those most at risk of anaphylaxis.
But blocking PAF is not always a good thing. Activation of platelets by PAF is vital for important bodily functions such as the clotting of blood at injury sites. It is important that drugs for the treatment of allergy do not interfere with other crucial actions of platelets. This has to be seriously considered when developing drugs.
Further Reading: Vadas, P. et al (2013) “Platelet-activating factor, histamine and tryptase levels in human anaphylaxis” Journal of Allergy and Clinical Immunology 131 (1) 144-49.