Inflammation and resolution in exercise-induced skeletal muscle injury: The effect of NSAID treatment on pro-inflammatory and anti-inflammatory/pro-resolving lipid mediators.
Current approaches in the treatment of exercise-induced muscle injury rely on the inhibition of pro-inflammatory pathways to alleviate cardinal signs of inflammation; redness, swelling, heat and pain. However, recent research suggests that the cellular events which occur early in acute inflammation engage an active and coordinated inflammatory resolution program characterised by a switch from pro-inflammatory mediators to production of active pro-resolution factors that govern the withdrawal of inflammation whilst facilitating tissue healing. This led to the identification of novel classes of anti-inflammatory/pro-resolving lipid mediators, including the lipoxins (LX), resolvins (Rv), and protectins (P), which may provide new targets in the treatment of inflammation. METHODS: Sixteen untrained male subjects (age 23±0.7yr, mass 88±3.1kg) were assigned to a placebo (PLA) (n=8) or ibuprofen (IBU) (n=8) group. Subjects completed a single bout of resistance exercise consisting of 3 sets of 8-12 repetitions of a squat, leg press and leg extensions at 80% 1RM. Intravenous blood samples were obtained at rest, at 30 min intervals between 0 and 3 h and again at 24 h post exercise. The IBU group orally consumed 400mg of the non-steroidal anti-inflammatory drug (NSAID) ibuprofen pre-exercise, and again at 5 and 10 h post exercise (1200 mg/day). Serum lipid mediator profiles were analysed via LC-MS targeted lipidomics. RESULTS: Acute exercise increased serum levels of pro-inflammatory eicosanoid species derived from both the COX-1 and 2 (prostaglandins: e.g. PGF2α, PGE2, PGD2, TXB2) and 5-LOX (leukotrienes: e.g. LTB4, LTB5) pathways. Additionally, heightened circulating levels of novel pro-resolving lipid mediators derived from arachidonic acid (LXA4 and LXB4), EPA (RvE1) and DHA (RvD1 andPD1 isomer) were detected post-exercise. Both the pro-inflammatory COX-1 & 2/5-LOX responses, as well as pro-resolving lipid mediator biosynthesis were blunted by the administration of the COX-1 and 2 inhibiting NSAID ibuprofen. CONCLUSION: Pro-inflammatory eicosanoids as well as novel pro-resolving bioactive lipid mediators are acutely up regulated following unaccustomed resistance exercise; a response which is diminished by IBU treatment. We hypothesize that the active resolution of exercise-induced inflammation may be important in effective post-exercise recovery and that a shift from anti-inflammatory interventions towards those which promote active resolution may hasten natural withdrawal of inflammation whilst facilitating the successful repair and regeneration of damaged muscle tissue
