Identification and structure elucidation of the pro-resolving mediators provides novel leads for resolution pharmacology

Abstract

Inflammatory diseases are a major socio-economic burden, with the incidence of such conditions on the rise, especially in western societies. For decades, the primary treatment paradigm for many of these conditions was to develop drugs that inhibit or antagonize the production and biological actions of molecules that were thought to be the culprits in propagating disease; these include cytokines and eicosanoids. This approach is effective in controlling disease propagation; however, long-term exposure to these anti-inflammatories is also associated with many side effects, some of which are severe, including immune-suppression. The discovery that termination of self-limited acute inflammation is an active process orchestrated by endogenous mediators, including the essential fatty acid-derived resolvins, protectins and maresins, has provided novel opportunities for the design of therapeutics that control inflammation with a lower burden of side effects. This is because at variance to anti-inflammatories, pro-resolving mediators do not completely inhibit inflammatory responses; instead, these mediators reprogramme the immune response to accelerate the termination of inflammation, facilitating the regain of function. The scope of this review is to highlight the biological actions of these autacoids and their potential utility as lead compounds in developing resolution pharmacology-based therapeutics. LINKED ARTICLES: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.