Abstract
Resolvins, maresins, and protectins can be formed from fish oils. These specialized pro-resolving mediators (SPMs) have been implicated in the resolution of inflammation. Synthetic versions of such SPMs exert anti-inflammatory effects in vitro and when administered to animal models. However, their importance as endogenous products formed in sufficient amounts to exert anti-inflammatory actions in vivo remains speculative. We biased our ability to detect SPMs formed in healthy volunteers by supplementing fish oil in doses shown previously to influence blood pressure and platelet aggregation under placebo-controlled conditions. Additionally, we sought to determine the relative formation of SPMs during an acute inflammatory response and its resolution, evoked in healthy volunteers by bacterial lipopolysaccharide (LPS). Bioactive lipids, enzymatic epoxyeicosatrienoic acids (EETs), and free radical-catalyzed prostanoids [isoprostanes (iPs)] formed from arachidonic acid and the fish oils, served as comparators. Despite the clear shift from ω-6 to ω-3 EETs and iPs, we failed to detect a consistent signal, in most cases, of SPM formation in urine or plasma in response to fish oil, and in all cases in response to LPS on a background of fish oil. Our results question the relevance of these SPMs to the putative anti-inflammatory effects of fish oils in humans.
Highlights
Resolvins, maresins, and protectins can be formed from fish oils
This article is available online at http://www.jlr.org of exogenous specialized proresolving mediator (SPM) in these models, are substantial; 0.6 g resolvin (Rv)D1 per mouse, for example, was used to attenuate the lipopolysaccharide (LPS)-induced inflammatory response in lung [18]. These quantities are in marked contrast to the low picograms per milliliter concentrations reported in humans [19]
Three subjects deviated from the supplementation regimen of seven capsules LovazaTM tid; that is, subject identification number (ID#) 31 took six capsules instead of seven on four occasions; morning dose on days 5 and 10 of supplementation, evening dose on day 8, and midday dose on day 12 during the 24 day dosing period due to difficulties in swallowing the capsules
Summary
Maresins, and protectins can be formed from fish oils These specialized pro-resolving mediators (SPMs) have been implicated in the resolution of inflammation. It has been speculated that cardiovascular benefit might derive, in part, from anti-inflammatory actions of fish oils: families of bioactive lipids which favor resolution of inflammation have been suggested to be of particular importance [13]. Synthetic versions of such specialized pro-resolving mediators (SPMs), products of transcellular metabolism of fish oils, exert anti-inflammatory effects in vitro and when administered in vivo in several animal models [14,15,16,17].
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