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Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment.

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AJP Regulatory Integrative and Comparative Physiology

Published online on

Abstract

Classical pro-inflammatory, and more recently discovered lipid mediators with pro-resolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. We investigated lipid mediator responses to resistance exercise and treatment with the non-steroidal anti-inflammatory drug (NSAID) ibuprofen. Human subjects undertook a single bout of resistance exercise (80% 1RM) following oral ingestion of ibuprofen (400 mg) or placebo control. Blood was collected during early recovery (0-3 h and 24 h post-exercise) and serum lipid mediator composition analyzed by LC-MS based targeted lipidomics. Post-exercise recovery was characterized by elevated levels of cyclooxygenase (COX-1 and 2) derived prostanoids (TXB2, PGE2, PGD2, PGF, PGI2), lipooxygenase (5-, 12-, and 15-LOX) derived hydroxyeicosatetraenoic acids (HETEs) and leukotrienes (e.g. LTB4), and epoxygenase (CYP) derived epoxy/dihydroxyeicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of lipid mediators with anti-inflammatory and pro-resolving properties including AA derived lipoxins (LXA4 & LXB4), and the EPA (E-series) and DHA (D-series) derived resolvins (RvD1 & RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen blocked increases in COX-1 and 2 derived prostanoids, but also resulted in off target reductions in leukotriene biosynthesis, and a diminished pro-resolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated post-exercise 5,6- and 8,9- DiHETrE only in those receiving ibuprofen. These findings characterize the lipid mediator response to resistance exercise in humans and show that pro-inflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by pro-resolving lipid mediators during post-exercise recovery.