Inflammation resolution and specialized pro-resolving lipid mediators in chronic rhinosinusitis

Abstract

Introduction: In chronic rhinosinusitis (CRS), a complex pathophysiology results from varied pro-inflammatory stimuli but is consistently characterized by classic cellular, molecular, and microbial alterations. Normally, endogenous specialized pro-resolving mediators (SPM) actively promote resolution of inflammation through numerous pathways, including those involved in host antimicrobial defense. However, these pathways appear to be disrupted in CRS.

Areas covered: This paper describes features of CRS in the context of chronic tissue inflammation, and potential mechanisms by which specialized pro-resolving mediators promote active resolution of tissue inflammation.

Expert opinion: Temporal phases of resolution must be tightly regulated to successfully resolve inflammation in CRS while preserving tissue functions such as barrier maintenance and special sensory function. Dysregulation of SPM enzymatic pathways has been recently shown in CRS and is associated with disease phenotypes and microbial colonization patterns. Current research in animal models and in vitro human cell culture, as well as human dietary studies, demonstrate relevant changes in cell signaling with lipid mediator bioavailability. Further clinical research may provide insight into the therapeutic value of this approach in CRS.

Keywords: LXA4; RvD1; RvD2; airway disease; chronic rhinosinusitis; lipoxin; mucosal inflammation; specialized pro-resolving mediators.

Figure 1.. Phases of inflammation and resolution.

Inflammation requires an active resolution phase that is carefully coordinated. Pro-inflammatory signaling molecules such as prostaglandins and leukotrienes dominate the onset of inflammation, while pro-resolving mediators such as lipoxins and resolvins play a vital role in restoring the site of the insult back to a healthy physiological state (green timeline). The imbalance of pro-inflammatory and pro-resolving mechanisms can lead to chronic, unresolved inflammation (red timeline). Original figure reproduced from Ref. 79.

Figure 2.. Lipid mediators derived from PUFAs.

Omega-3 fatty acid-derived pro-resolving lipid mediators are produced from endogenous eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), or docosahexaenoic acid (DHA). A variety of enzymes and intermediates create these specialized pro-resolving mediators in the resolution of inflammation. Original figure reproduced from Ref. 80.

Figure 3.. Balanced approach to chronic inflammatory disease treatment, where anti-inflammatory strategies are complemented by endogenous pro-resolving mechanisms.

Chronic rhinosinusitis has been shown to have an increased prevalence in patients with dysfunction of the inflammatory process. To properly resolve this inflammation pro-inflammatory, anti-inflammatory, and pro-resolving processes must be balanced and temporally coordinated to restore a healthy physiological state.