Abstract
Skeletal muscle responds to exercise-induced damage by orchestrating an adaptive process that protects the muscle from damage by subsequent bouts of exercise, a phenomenon called the repeated bout effect (RBE). The mechanisms underlying the RBE are not understood. We hypothesized that an attenuated inflammation response following a repeated bout of lengthening contractions (LC) would be coincidental with a RBE, suggesting a potential relationship. Fourteen men (n = 7) and women (n = 7) completed two bouts of lengthening contractions (LC) separated by 28 days. Muscle biopsies were taken before the first bout (B1) from the non-exercised leg, and from the exercised leg 2- and 27-d post-B1 and 2-d following the second bout (B2). A 29-plex cytokine array identified alterations in inflammatory cytokines. Immunohistochemistry quantified inflammatory cell infiltration and major histocompatibility complex class 1 (MHC-1). Muscle soreness was attenuated in the days following B2 relative to B1, indicating a RBE. Intramuscular monocyte chemoattractant protein (MCP1) and interferon gamma-induced protein 10 (IP10) increased following B2 relative to the pre-exercise sample (7–52 and 11–36 pg/ml, respectively p < 0.05). Interleukin 4 (IL4) decreased (26–13 pg/ml, p < 0.05) following B2 relative to the pre-exercise sample. Infiltration of CD68+ macrophages and CD8+ T-cells were evident following B2, but not B1. Moreover, CD8+ T-cells were observed infiltrating apparently necrotic muscle fibers. No changes in MHC-1 were found. We conclude that inflammation is not attenuated following a repeated bout of LC and that CD8+ T-cells may play a role in muscle adaptation following LC. Moreover, it appears that the muscle or the immune system becomes sensitized to an initial bout of damaging exercise such that inflammatory cell infiltration into the muscle is enhanced upon a repeated bout of damaging exercise.
Highlights
A truly remarkable property of skeletal muscle is that it maintains an intrinsic protective mechanism, whereby it swiftly adapts following exercise-induced damage, making it capable of resisting future damage
Consistent with others (Stupka et al, 2001; Mackey et al, 2011) we observed a significant increase in macrophage content in the muscle following damaging exercise, though we are the first, to our knowledge, to report that macrophages accumulate in greater numbers following a second exposure to lengthening contractions (LC)
The significant increase in T-cells observed after B2 in the present study suggests that these cells may play a role in the adaptive and regenerative processes of healthy human skeletal muscle to damaging exercise
Summary
A truly remarkable property of skeletal muscle is that it maintains an intrinsic protective mechanism, whereby it swiftly adapts following exercise-induced damage, making it capable of resisting future damage. This phenomenon has been recognized for over half a century (Highman and Altland, 1963) and is commonly referred to in the literature as the repeated bout effect. Muscle Inflammation and the Repeated Bout Effect (RBE) (Nosaka and Clarkson, 1995). Inflammation has not been comprehensively assessed following repeated bouts of damaging exercise in humans, leaving doubt as to whether this mechanism is important in mediating the protective effect in human skeletal muscle. Information from these studies is somewhat limiting given that the cytokines were measured only at the mRNA level (Hubal et al, 2008; Mackey et al, 2011)
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