Novel approaches to the inhibition of mast cells in allergic disease

摘要

IgE-mediated allergic disease is a global health burden and major drain on healthcare resources [1, 2]. Allergic-disease can present in many ways depending on the tissues affected, from acute life-threatening episodes of anaphylaxis due to food allergy, the strictly seasonal symptoms due to grass pollen-induced summer rhinocon-junctivitis (hayfever), or the chronic on-going inflammation evident in bronchial asthma. Current treatment approaches for these common diseases are often of poor efficacy or have unacceptable side-effects, and there is therefore an unmet need for novel inhibitors of allergic disease. Mast cells play a central role in the pathophysiol-ogy of allergy through their ability to release a plethora of pro-inflammatory autacoid mediators, proteases and cy-tokines in response to both high-affinity IgE receptor (FceRI)-dependent and -independent activation [3]. Within diseased tissues, mast cells relocate to key tissue structures such as the airway smooth muscle [4] and mucous glands [5] in asthma, facilitating the specific targeting of their mediators and adhesive cell-cell signals to these dysfunctional airway elements. Targeting mast cell activation therefore has the potential to attenuate allergic disease.