Specialized pro-resolving mediators exist at the heart of the physiological response vital for resolving inflammation. Inadequate inflammation resolution builds a foundation for a plethora of chronic conditions, and thus fully understanding and appreciating the role of specialized pro-resolving mediators in homeostasis is critical for addressing these conditions. Specialized pro-resolving mediators are derived from omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and they include resolvins, maresins, protectins, and lipoxins.
What Are Specialized Pro-resolving Mediators?
Primarily, specialized pro-resolving mediators promote the resolution phase of inflammation, subsequently playing a role in host defense, organ protection, and tissue remodeling. They also initiate physiological changes at the inflammation site by ending neutrophil infiltration and by promoting macrophage uptake of apoptotic cells.1-2
Secondarily, these mediators keep pro-inflammatory mediators (e.g. eicosanoids, chemokines, and cytokines) in check, regulate specific microRNA activity, and enhance microbial killing.3-4
Why Care About Specialized Pro-resolving Mediators?
The resolution phase of inflammation prevents inflammation from turning into excessive chronic inflammation, leading to a variety of conditions like vascular disease, metabolic syndrome, and neurological diseases.1
Phases of Inflammation
Phase 1: Initiation Phase
Pro-inflammatory lipid mediators derived from polyunsaturated omega-6 arachidonic acid (ARA) and various cytokines and chemokines initiate inflammation.1 Lipid mediators, cytokines, chemokines, and complement components stimulate chemotaxis to move neutrophils into necessary tissues to break down and neutralize invaders through phagocytosis.1
Phase 2: Resolution Phase
Receptor antagonists resolve inflammation. Specialized pro-resolving mediators prevent neutrophils from continuing to enter tissues and promote macrophages to clear cellular debris.1 When inflammation resolution fails, inflammation will become excessive and chronic.1
Other Important Players
Prostaglandins and leukotrienes are eicosanoid pro-inflammatory lipid mediators important for vascular responses and neutrophils and monocytes exiting the circulation.1 Prostaglandins, along with leukotrienes, are produced from arachidonic acid (AA), and are necessary to activate the resolution phase of inflammation.5 Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin biosynthesis, which in turn may inhibit the activation of the resolution phase.1
Microparticles are membrane-derived vesicles produced by self-resolving exudates, and they have anti-inflammatory and pro-resolving capacities.1 Microparticles also enhance macrophage clearing of debris during resolution and enhance specialized pro-resolving mediator biosynthesis.
M2 Macrophages are pro-resolving white blood cells that support specialized pro-resolving mediator production and engulf apoptotic neutrophils.3 Activation of macrophages is an essential step towards the resolution of inflammation.3 Eosinophils are white blood cells specific to parasitic infections and allergic responses, and they support specialized pro-resolving mediator production.1