Does Muscle-Derived Interleukin-6 Mediate Some of the Beneficial Effects of Exercise on Cancer Treatment-Related Fatigue?

Abstract

Purpose/Objectives To review evidence that muscle-derived interleukin-6 (IL-6) mediates some of the beneficial effects of exercise on cancer treatment–related fatigue (CTRF). Data Sources Electronic nursing, psychology, and medicine databases. Data Synthesis Fatigue is a common and often debilitating symptom associated with cancer treatment. Although the molecular mechanisms underlying CTRF have yet to be fully elucidated, it may be akin to the fatigue associated with “sickness behavior,” which is initiated by the production of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). Physical exercise has been shown to decrease fatigue levels in patients with cancer undergoing treatment. Skeletal muscle selectively produces IL-6 during exercise, and muscle-derived IL-6 can decrease the production and activity of IL-1β and TNF-α. Thus, the anti-inflammatory effects of muscle-derived IL-6 may be a mechanism underlying the observed beneficial effects of exercise on CTRF. Conclusions Further studies are needed to determine whether the anti-inflammatory effects of exercise underlie its beneficial effects on CTRF. Implications for Nursing Nurses have proven to be leaders in the field of cancer symptom management. An understanding of potential mechanisms underlying the beneficial effects of exercise on CTRF may help to fine-tune exercise interventions to maximize symptom control and to identify new treatment strategies for fatigued patients with cancer who are unable to participate in an exercise program.

Effect of flaxseed supplementation and exercise training on lipid profile, oxidative stress and inflammation in rats with myocardial ischemia

“…This has been in correlation with the elevated levels of tissue mRNA expression and circulating PTX 3 reported in a model of acute myocardial infarction which was explained by the role played by interleukin-1R-MyD88 in inducing PTX 3 transcript after ischemia. [12,41,42]. A significant increase of plasma PTX 3 was observed in group IV that were receiving flaxseed supplementation and on exercise (0.35±0.11ng/ml) as compared to group I the control group (0.15±0.04 ng/ml) and to group III that was on flaxseed supplementation only (0.18±0.12 ng/ml) (P< 0.001, P< 0.001 respectively).…”

“…Recent research reported that moderate endurance activity influenced circulating cytokine levels specially the TNF- α levels which could be due to production of IL-6 produced by exercising muscle as an anti-inflammatory effect [41]. …”

Biomarkers of peripheral muscle fatigue during exercise

“…Myofibrils also release mechano-growth factors, which impart autocrine effects on the muscle fibre. Relevant inflammatory biomarkers are catabolic biomarkers [18] and include cells involved in the cellular immune response, pro-inflammatory cytokines, such as ILs, IL-receptor antagonists (IL-RA), TNF-α [76] and other markers of inflammation [18]. …”

“…In 19 patients with CFS, who were studied during a 25 min cycling exercise to determine the amount of mRNA of metabolite-detecting genes (ASIC3, P2X4, P2X5), adrenergic genes (A2A, B-1, B-2, COMT) and immune system genes (IL-6, IL-10, TNF-α, TLR4, CD14), the activity of the genes encoding for ASIC3, P2X4, P2X5, B-1, B-2, COMT, IL-10, TLR4 and CD14 increased significantly in blood lymphocytes 30 min, 24 h and 48 h post-exercise [91]. The gene activity persistently increased between 0.5-48 h after exercise [91], suggesting that dysregulation of metabolite-detecting receptors occurs during fatigue [76,92]. In a study of subjects exposed to exhaustive exercise, both serum IL-6 and muscle IL-6 mRNA increased [93].…”

Role of nuclear factor-κB-mediated inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents

“…102 Furthermore, muscle-derived IL-6 has been proposed as a mechanism for the beneficial effects of exercise against cancer treatment-related fatigue. 103 …”