Although reporting significant within and between group differences, in none of the RCTs’ relationships between changes in inflammatory markers and muscle performance were reported. Only Ogawa et al.[40▪] described a correlation between the relative change in CRP (significant decrease) and TNF-α (nonsignificant decrease) and the relative change in subscapular muscle thickness, suggesting (but not demonstrating) a causal relationship.
The use of an acute bout of exercise to induce an increase in circulating inflammatory cytokines in Beavers et al.[36▪] points to an interesting paradigm: an acute inflammatory response has beneficial effects, contributing to protection and repair, whereas chronic, long-standing inflammation is detrimental . In addition, the acute inflammatory response to unaccustomed exercise-induced muscle damage does not preclude a beneficial effect of repeated long-term exercise on the basal inflammatory profile. Therefore, outcomes may vary with respect to the time point after the last exercise session at which inflammation is measured and the intensity of exercise used.
Furthermore, one study showed comparable postexercise increases in IL-6 in old and young patients [15▪]. In the light of known benefits of short-term inflammation in tissue repair, decreases in exercise-induced serum levels and in LPS-induced monocytic expression of IL-6 [41▪] may not necessarily represent a beneficial effect on CLIP, but rather reflect a decreased immunity following heavy exertion  or a lower level of exercise-induced muscle damage in well trained muscles. However, exercise-induced IL-6 release acts in a hormone-like fashion, increasing glucose uptake and fatty acid oxidation locally and inducing hepatic glucose production and adipose tissue lipolysis . Lesser increases after exercise may, therefore, also reflect muscular adaptations in energy metabolism.
One RCT compared nutritional supplements using soy (rich in isoflavones and leucin) or milk supplements during 4 weeks and could not identify a beneficial effect on eccentric exercise-induced systemic inflammation [36▪]. It is supposed that a high-quality protein diet, consisting of repeated small amounts of total protein (<30 g/intake) rich in essential amino acids, as well as vitamin D supplementation, alone or in association with resistance training, may have beneficial effects on CLIP and sarcopenia (for review see ).
No recent studies have been identified with respect to drug treatment of CLIP and sarcopenia. Potential pharmaceutical interventions include IL-6 and CRP lowering statins, angiotensin-converting enzyme inhibitors (reducing proteolytic effects of angiotensin II that inhibits phosphorylation of Forkhead box O3 (transcription factor, FOXO-3) and stimulates caspase-3), TNF-α inhibitors, nitric oxide donors (acting as calpain inhibitor), and PPAR-α agonists (downregulating NFκB) (for review see [2,48–50]). However, unless the drug can specifically be targeted to muscle tissue, major side-effects are to be expected. Targeting muscle-specific transcription factors such as MyoD, myogenin, MRF4 and myf-5 that decrease during the ageing process and are negatively influenced by TNF-α  might be promising. NSAIDs that may be useful in muscle weakness associated with acute inflammatory conditions  (I. Beyer et al., unpublished observation) have not yet shown clear benefits on CLIP .
Recent research strengthens CLIP's relationship with sarcopenia, with TNF-α and IL-6 as most reported inflammatory parameters. Adiposity contributes to CLIP and new studies should take fat mass into account. Underlying mechanisms are progressively unravelled, including oxidative and proteolytic pathways. Physical exercise seems the best intervention to reduce CLIP and counter sarcopenia. However, IL-6 is also released during exercise as an energy-signalling molecule, in a hormone-like fashion unrelated to inflammation, and exercise-induced changes in IL-6 require careful interpretation. To date, an optimal amount of exercise remains elusive, and more research is warranted to unravel the exact dose–response relationship.
Papers of particular interest, published within the annual period of review, have been highlighted as:
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 93).
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