Endocrine Abstracts

Inflammation is a primordial response to infection and injury that seeks to neutralise and eliminate foreign organisms and/or material. Thus, inflammation is no trivial event. Life depends upon it. In general, the innate inflammatory response initiates within minutes and resolves within hours. Chronic inflammation, on the other hand, persists for weeks, months or even years and, unlike the acute response, is the side of host immunity we need to avoid. Notwithstanding, dispersed among this black and white view of inflammation are shades of grey. We are constantly reminded that defining inflammation is not so easy and that while acute inflammation can resolve, it can also be recurrent and that, over time, chronic inflammation can also resolve or persist with devastating consequences to the host. In this presentation, one of these many aspects of the inflammatory response – how acute inflammation resolves, will be discussed. In doing so it will be argued that resolution is as active process, whose failure may predispose the host to chronic inflammatory diseases and autoimmunity. At the very least it is hoped we can highlight resolution as a critical facet of the inflammatory response and serve to underline the importance of not altering its normal course of action when developing novel anti-inflammatory drugs. Ultimately, it will be proposed here that resolution is controlled by endogenous pro-resolution factors, which, for the future, may represent a treasure trove for drug discovery in terms of designing drugs that mimic their mode of action or enhance their synthesis. Specifically, I will recount the earlier work done on cyclooxygenase and lipoxygenase-derived lipid mediators (cyclopentenone prostaglandins, prostaglandin D₂, lipoxins and aspirin-triggered epi-lipoxins) in limiting the continuity of the inflammatory response; bring the audience up to date with a more recent understanding of some of the cellular players in this setting and introduce some new soluble mediators (resolvins) and their receptors as potentially novel pro-resolving agents. In this setting, macrophage phenotype as a critical determinant of inflammation longevity will also be discussed.