MedicinesHost Response with Novel Nanoproresolving Inflammation in Mice: Reprogramming the Aging Delays Resolution of Acute

Aging is associated with an overt inflammatory phenotype and physiological decline. Specialized proresolving lipid mediators (SPMs) are endogenous autacoids that actively promote resolution of inflammation. In this study, we investigated resolution of acute inflammation in aging and the roles of SPMs. Using a self-resolving peritonitis and resolution indices coupled with lipid mediator metabololipidomics, we found that aged mice had both delayed resolution and reduced SPMs. The SPM precursor docosahexaenoic acid accelerated resolution via increased SPMs and promoted human monocyte reprogramming. In aged mice, novel nanoproresolving medicines carrying aspirin-triggered resolvins D1 and D3 reduced inflammation by promoting efferocytosis. These findings provide evidence for age-dependent resolution pathways in acute inflammation and novel means to activate resolution. The Journal of Immunology , 2014, 193: 000–000. age is associated with heightened proinflammatory status with elevated levels of TNF- a , IL-1 b , and IL-6, which contribute to the age-related decline of physiological functions (8). There-fore, we hypothesized that endogenous resolution programs and specifically proresolving lipid mediators may be dysregulated during aging. To address this, in the present study we used a systems approach with LM metabololipidomics to investigate whether age impacts resolution of acute inflammation. Our findings demonstrated in aged mice that exudate SPMs are reduced, inflammation is heightened, and resolution is delayed. This resolution delay was rescued with SPMs (i.e., RvD3), SPM precursors, and nano-proresolving medicine (NPRM) carrying aspirin-triggered (AT) RvD1 and AT-RvD3 (Resolvin-NPRM).

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