D-series resolvins
RvD is a polyhydroxy metabolite of DHA. To date, six RvDs with different positions of cis-trans isomers, as well as the number, position and chirality of the hydroxyl residues have been discovered. D-series Rvs (RvD1-RvD6) are biosynthesized from DHA by the LOX in PMN and macrophages (Serhan et al. 2002). Hydrolysis of peroxide intermediates derived from two LOXs in DHA produces RvD1 and RvD2. On the other hand, the reduction of the peroxide intermediates produces RvD5 (Serhan et al. 2002). In hypoxic endothelial cells in the presence of aspirin, COX-2 converts DHA to 13-hydroxy-DHA or 17R-hydroxy-DHA and activated PMN converts these products to AT-RvD1, AT-RvD2, and other AT-RvD-series. RvD3 and RvD4 are produced through hydrolysis of 4S-hydroperoxy-17S-hydroxy-docosahexaenoic acid, whereas RvD6 is derived from peroxidase of the same precursor.
In a peritonitis model, the in vivo RvD3 levels after zymosan A challenge increases significantly up to 48 hours after inflammation initiation, while RvD1, RvD2, and RvD5 peak at the early stages of the inflammation termination phase (6–24 hours) (Dalli et al. 2013b). RvD3 appears to be produced by a subpopulation of macrophages with high 15-LOX activity (Dalli et al. 2013b). In vivo production of RvD4 in an Staphylococcus aureus injected the dorsal pouch infection model continues for more than 72 hours after sustained release, suggesting that RvD is produced continuously and is under different control from other Rvs (Winkler et al. 2016). RvD6 kinetics have not been reported yet.