Unaccustomed exercise consisting of eccentric (i.e., lengthening) muscle contractions often results in muscle damage characterized by ultrastructural alterations in muscle tissue, clinical signs, and symptoms (e.g., reduced muscle strength and range of motion, increased muscle soreness and swelling, efflux of myocellular proteins). The time course of recovery following exercise-induced muscle damage depends on the extent of initial muscle damage, which in turn is influenced by the intensity and duration of exercise, joint angle/muscle length, and muscle groups used during exercise. The effects of these factors on muscle strength, soreness, and swelling are well characterized. By contrast, much less is known about how they affect intramuscular inflammation and molecular aspects of muscle adaptation/remodeling. Although inflammation has historically been viewed as detrimental for recovery from exercise, it is now generally accepted that inflammatory responses, if tightly regulated, are integral to muscle repair and regeneration. Animal studies have revealed that various cell types, including neutrophils, macrophages, mast cells, eosinophils, CD8 and T-regulatory lymphocytes, fibro-adipogenic progenitors, and pericytes help to facilitate muscle tissue regeneration. However, more research is required to determine whether these cells respond to exercise-induced muscle damage. A large body of research has investigated the efficacy of physicotherapeutic, pharmacological, and nutritional interventions for reducing the signs and symptoms of exercise-induced muscle damage, with mixed results. More research is needed to examine if/how these treatments influence inflammation and muscle remodeling during recovery from exercise.

The notion that prolonged, intense exercise causes an “open window” of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8⁺T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes.

Aging is associated with a vasoconstrictive, pro-coagulant, and pro-inflammatory profile of arteries and a decline in the bioavailability of the endothelium-derived molecule nitric oxide. Dietary nitrate elicits vasodilatory, anti-coagulant and anti-inflammatory effects in younger individuals, but little is known about whether these benefits are evident in older adults. We investigated the effects of 140 mL of nitrate-rich (HI-NI; containing 12.9 mmol nitrate) versus nitrate-depleted beetroot juice (LO-NI; containing ≤0.04 mmol nitrate) on blood pressure, blood coagulation, vascular inflammation markers, plasma nitrate and nitrite before, and 3 h and 6 h after ingestion in healthy older adults (five males, seven females, mean age: 64 years, age range: 57–71 years) in a randomized, placebo-controlled, crossover study. Plasma nitrate and nitrite increased 3 and 6 h after HI-NI ingestion (p < 0.05). Systolic, diastolic and mean arterial blood pressure decreased 3 h relative to baseline after HI-NI ingestion only (p < 0.05). The number of blood monocyte-platelet aggregates decreased 3 h after HI-NI intake (p < 0.05), indicating reduced platelet activation. The number of blood CD11b-expressing granulocytes decreased 3 h following HI-NI beetroot juice intake (p < 0.05), suggesting a shift toward an anti-adhesive granulocyte phenotype. Numbers of blood CD14⁺⁺CD16⁺ intermediate monocyte subtypes slightly increased 6 h after HI-NI beetroot juice ingestion (p < 0.05), but the clinical implications of this response are currently unclear. These findings provide new evidence for the acute effects of nitrate-rich beetroot juice on circulating immune cells and platelets. Further long-term research is warranted to determine if these effects reduce the risk of developing hypertension and vascular inflammation with aging.

Reprogramming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. This study investigated the time course-dependent changes in the muscular transcriptome after an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Skeletal muscle samples were taken at baseline, 3 h, 48 h, and 96 h postexercise from eight healthy, endurance-trained men. RNA was extracted from muscle. Differential gene expression was evaluated using Illumina microarrays and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Three hours postexercise, 102 gene sets were upregulated [family wise error rate (FWER), P < 0.05], including groups of genes related with leukocyte migration, immune and chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1 signaling. Forty-eight hours postexercise, among 19 enriched gene sets (FWER, P < 0.05), two gene sets related to actin cytoskeleton remodeling were upregulated. Ninety-six hours postexercise, 83 gene sets were enriched (FWER, P < 0.05), 80 of which were upregulated, including gene groups related to chemokine signaling, cell stress management, and extracellular matrix remodeling. These data provide comprehensive insights into the molecular pathways involved in acute stress, recovery, and adaptive muscular responses to endurance exercise. The novel 96 h postexercise transcriptome indicates substantial transcriptional activity potentially associated with the prolonged presence of leukocytes in the muscles. This suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 h after endurance exercise involving muscle damage.