Some people have allergic reactions to certain substances that can be so pronounced that they affect the entire body. Such a reaction − called anaphylaxis − can be so severe that it becomes life-threatening. An injection of adrenalin is currently the only effective remedy known for this condition. But adrenalin often has no, or insufficient, effect on the cardiovascular collapse that is a consequence of the allergic shock.
Anaphylaxis occurs fairly frequently and strikes up to 15% of the population. It can be caused by a bee sting, by medications, by contact with latex, or by certain foods such as peanuts. Because more and more people are being confronted with anaphylactic shock, and given the limitations of the current treatment methods, scientists are searching for better remedies.
Several leading actors
Scientists are aware of the possible role of PAF (Platelet Activating Factor) in blood pressure and heart disorders that result from shock like anaphylactic shock. They also know that extreme amounts of nitric oxide (NO) can lie at the basis of shock. The so-called NOS enzymes are responsible for the production of NO in the body. However, the role of NO in producing anaphylactic shock, or how shock is induced by PAF, has always been unclear. So, Anje Cauwels and her colleagues, under the leadership of Peter Brouckaert, have been focusing their attention on anaphylaxis to try to shed more light on these matters.
The mechanism exposed
The Ghent researchers used mice to study PAF and anaphylactic shock. To their great surprise, the hyper-acute PAF-induced shock was completely dependent on NO. Furthermore, the production of NO was not regulated by iNOS (the expected activator) but by the constitutive eNOS, which is activated via the PI3K pathway. Up to now, scientists have thought that this pathway only plays a role in normal blood pressure regulation, and not in shock.
The research team then set out to verify whether inhibition of the several leading actors could prevent anaphylactic shock. And indeed, from their research it turns out that inhibition of eNOS or PI3K provides total protection.
New perspectives for future therapies
The research of Cauwels and Brouckaert has yielded an unexpected new finding: namely, that eNOS-derived NO plays a key role in anaphylactic shock. This discovery opens new perspectives for treatment − it's now clear that eNOS and PI3K are prime targets for new drugs against anaphylaxis.