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Abstract
Because inflammation is appreciated as a unifying basis of many widely occurring diseases,
the mechanisms involved in its natural resolution are of considerable interest. Using
contained, self-limited inflammatory exudates and a systems approach, novel lipid-derived
mediators and pathways were uncovered in the resolution of inflammatory exudates.
These new families of local mediators control both the duration and magnitude of acute
inflammation as well as the return of the site to homeostasis in the process of catabasis.
This new genus of specialized proresolving mediators (SPM) includes essential fatty
acid-derived lipoxins, resolvins, protectins, and, most recently, maresins. These
families were named based on their unique structures and potent stereoselective actions.
The temporally initiated biosynthesis of SPM and their direct impact on leukocyte
trafficking and macrophage-directed clearance mechanisms provide clear evidence that
resolution is an active, programmed response at the tissue level. Moreover, SPM that
possess anti-inflammatory (ie, limiting PMN infiltration) and proresolving (enhance
macrophage uptake and clearance of apoptotic PMN and microbial particles) actions
as well as stimulating mucosal antimicrobial responses demonstrate that anti-inflammation
and proresolution are different responses of the host and novel defining properties
of these molecules. The mapping of new resolution circuits has opened the possibility
for understanding mechanisms that lead from acute to chronic inflammation, or to the
resolution thereof, as well as to potential, resolution-based immunopharmacological
therapies.