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:

• airway disease
• chronic rhinosinusitis
• lipoxin
• LXA4
• mucosal inflammation
• RvD1
• RvD2
• specialized pro-resolving mediators

Article highlights

• Resolution of inflammation is an active process that requires precise temporal regulation. Disruption of this process can contribute to disease chronicity

• Chronic rhinosinusitis (CRS) patients exhibit dysregulation of specialized pro-resolving mediators when compared to healthy subjects

• Specialized pro-resolving mediators are derived from omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). Dietary supplementation of omega-3 PUFAs results in increased availability of precursors for these important mediators

• Not all signaling molecules are exclusively pro-inflammatory or anti-inflammatory. Molecules such as prostaglandin E2 (PGE2) have roles in both the initiation and resolution of inflammation

• One class of SPMs, resolvins, carries a significant role in allergic inflammation by reducing both IgE class switching and type II inflammation, thus limiting the eosinophilic environment commonly seen in CRS.

Declaration of interest

V Ramakrishnan has served as a consultant for Medtronic, Inc., and Optinose US, which are unaffiliated with the current study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer works in epithelial physiology in CRS. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This publication was supported by the National Institute On Deafness and Other Communication Disorders (NIDCD) of the National Institutes of Health under grant number K23-DC014747 (VRR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.