Effect of post-exercise protein–leucine feeding on neutrophil function, immunomodulatory plasma metabolites and cortisol during a 6-day block of intense cycling

Whey protein and leucine ingestion following exercise increases muscle protein synthesis and could influence neutrophil function during recovery from prolonged intense exercise. We examined the effects of whey protein and leucine ingestion post-exercise on neutrophil function and immunomodulators during a period of intense cycling. In a randomized double-blind crossover, 12 male cyclists ingested protein/leucine/carbohydrate/fat (LEUPRO 20/7.5/89/22 g h−1, respectively) or isocaloric carbohydrate/fat control (CON 119/22 g h−1) beverages for 1–3 h post-exercise during 6 days of high-intensity training. Blood was taken pre- and post-exercise on days 1, 2, 4 and 6 for phorbol myristate acetate (PMA)-stimulated neutrophil superoxide (O2 −) production, immune cell counts, amino acid and lipid metabolism via metabolomics, hormones (cortisol, testosterone) and cytokines (interleukin-6, interleukin-10). During recovery on day 1, LEUPRO ingestion increased mean concentrations of plasma amino acids (glycine, arginine, glutamine, leucine) and myristic acid metabolites (acylcarnitines C14, myristoylcarnitine; and C14:1-OH, hydroxymyristoleylcarnitine) with neutrophil priming capacity, and reduced neutrophil O2 production (15–17 mmol O2 − cell−1 ± 90 % confidence limits 20 mmol O2 − cell−1). On day 2, LEUPRO increased pre-exercise plasma volume (6.6 ± 3.8 %) but haematological effects were trivial. LEUPRO supplementation did not substantially alter neutrophil elastase, testosterone, or cytokine concentrations. By day 6, however, LEUPRO reduced pre-exercise cortisol 21 % (±15 %) and acylcarnitine C16 (palmitoylcarnitine) during exercise, and increased post-exercise neutrophil O2 − (33 ± 20 mmol O2 − cell−1), relative to control. Altered plasma amino acid and acylcarnitine concentrations with protein–leucine feeding might partly explain the acute post-exercise reduction in neutrophil function and increased exercise-stimulated neutrophil oxidative burst on day 6, which could impact neutrophil-dependent processes during recovery from intense training

Adenosine regulation of the immune system

Adenosine is an endogenous nucleoside, released into the extracellular space in response to metabolic stress and cell damage and critically involved in the maintenance of tissue integrity by modulation of the immune system. The magnitude and duration of adenosine signaling are dictated by the expression and activity of a plethora of synthetic and catabolic enzymes as well as nucleoside transporters, which calibrate finely the concentration of this nucleoside in the biophase of specific receptors. Indeed, once released into the extracellular space, adenosine governs several aspects of immune cell functions by interaction with four G-protein-coupled cell membrane receptors, designated as A1, A2A, A2B, and A3 receptors. The engagement of such receptors, expressed heterogeneously on the surface of several immune cell populations, including neutrophils, macrophages, dendritic cells, mast cells, and lymphocytes, shapes a broad array of immune cell functions, which include cytokine production, degranulation, chemotaxis, cytotoxicity, apoptosis, and proliferation