Prostaglandin E2 in NSAID-exacerbated respiratory disease: protection against cysteinyl leukotrienes and group 2 innate lymphoid cells

Abstract

Purpose of review 

The purpose of this review is to describe the recent advances that have been made in understanding the protective role of prostaglandin E2 (PGE₂) in aspirin-exacerbated respiratory disease (AERD), known in Europe as NSAID-exacerbated respiratory disease (N-ERD).

Recent findings 

Decreased PGE₂ signaling through the EP₂ receptor in patients with AERD leads to an increase in leukotriene synthesis and signaling. Leukotriene signaling not only directly activates group 2 innate lymphoid cells and mast cells, but it also increases production of IL-33 and thymic stromal lymphopoietin. These cytokines drive Th2 inflammation in a suspected feed-forward mechanism in patients with AERD.

Summary 

Recent discoveries concerning the role of PGE₂ in leukotriene synthesis and signaling in AERD, as well as downstream effects on group 2 innate lymphoid cells and mast cells, allow for a more comprehensive understanding of the pathogenesis of this disease. These discoveries also identify new paths of potential investigation and possible therapeutic targets for AERD.