Inflammation and resolution in exercise-induced skeletal muscle injury: The effect of NSAID treatment on pro-inflammatory and anti-inflammatory/pro-resolving lipid mediators.

Authors

James F. Markworth, Liggins Institute, The University of Auckland, Auckland, New ZealandFollow
Luke Vella, School of Exercise and Nutrition Sciences, Deakin University, Victoria, Australia
Krishna R. Maddipati, Bioactive Lipids Research Program, Department of Pathology, School of Medicine, Wayne State University, Detroit, USA
David Cameron-Smith, Liggins Institute, The University of Auckland, Auckland, New ZealandFollow

Abstract

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. PGF_2α, PGE₂, PGD_2, 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.

Recommended Citation

Markworth, James F.; Vella, Luke; Maddipati, Krishna R.; and Cameron-Smith, David (2013) "Inflammation and resolution in exercise-induced skeletal muscle injury: The effect of NSAID treatment on pro-inflammatory and anti-inflammatory/pro-resolving lipid mediators.," International Journal of Exercise Science: Conference Proceedings: Vol. 10: Iss. 1, Article 34.
Available at: https://digitalcommons.wku.edu/ijesab/vol10/iss1/34