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      Cancer cachexia prevention via physical exercise: molecular mechanisms

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          Abstract

          Cancer cachexia is a debilitating consequence of disease progression, characterised by the significant weight loss through the catabolism of both skeletal muscle and adipose tissue, leading to a reduced mobility and muscle function, fatigue, impaired quality of life and ultimately death occurring with 25–30 % total body weight loss. Degradation of proteins and decreased protein synthesis contributes to catabolism of skeletal muscle, while the loss of adipose tissue results mainly from enhanced lipolysis. These mechanisms appear to be at least, in part, mediated by systemic inflammation. Exercise, by virtue of its anti-inflammatory effect, is shown to be effective at counteracting the muscle catabolism by increasing protein synthesis and reducing protein degradation, thus successfully improving muscle strength, physical function and quality of life in patients with non-cancer-related cachexia. Therefore, by implementing appropriate exercise interventions upon diagnosis and at various stages of treatment, it may be possible to reverse protein degradation, while increasing protein synthesis and lean body mass, thus counteracting the wasting seen in cachexia.

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          Most cited references188

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          Cellular survival: a play in three Akts.

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            IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans.

            The purpose of the present study was to test the hypothesis that a transient increase in plasma IL-6 induces an anti-inflammatory environment in humans. Therefore, young healthy volunteers received a low dose of recombinant human (rh)IL-6 or saline for 3 h. Plasma IL-6 levels during rhIL-6 infusion were approximately 140 pg/ml, corresponding to the levels obtained during strenuous exercise. The infusion of rhIL-6 did not induce enhanced levels of the proinflammatory cytokine TNF-alpha but enhanced the plasma levels of the two anti-inflammatory cytokines IL-1 receptor agonist (IL-1ra) and IL-10 compared with saline infusion. In addition, C-reactive protein increased 3 h post-rhIL-6 infusion and was further elevated 16 h later compared with saline infusion. rhIL-6 induced increased levels of plasma cortisol and, consequently, an increase in circulating neutrophils and a decrease in the lymphocyte number without effects on plasma epinephrine, body temperature, mean arterial pressure, or heart rate. In conclusion, this study demonstrates that physiological concentrations of IL-6 induce an anti-inflammatory rather than an inflammatory response in humans and that IL-6, independently of TNF-alpha, enhances the levels not only of IL-1ra but also of IL-10. Furthermore, IL-6 induces an increase in cortisol and, consequently, in neutrocytosis and late lymphopenia to the same magnitude and with the same kinetics as during exercise, suggesting that muscle-derived IL-6 has a central role in exercise-induced leukocyte trafficking.
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              Cachexia in cancer patients.

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                Author and article information

                Contributors
                D.Gould@wlv.ac.uk
                Journal
                J Cachexia Sarcopenia Muscle
                J Cachexia Sarcopenia Muscle
                Journal of Cachexia, Sarcopenia and Muscle
                Springer-Verlag (Berlin/Heidelberg )
                2190-5991
                2190-6009
                13 December 2012
                June 2013
                : 4
                : 2
                : 111-124
                Affiliations
                [ ]School of Sport, Performing Arts and Leisure, Department of Physical Activity, Exercise and Health, University of Wolverhampton, Walsall, West Midlands UK
                [ ]Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Russell’s Hall Hospital, Dudley, West Midlands UK
                [ ]Research Institute in Physical Performance and Rehabilitation, Centre for Research and Technology, Thessaly Trikala, Greece
                [ ]Department of Surgery, Dudley Group of Hospitals NHS Trust, Russell’s Hall Hospital, Dudley, West Midlands UK
                Article
                96
                10.1007/s13539-012-0096-0
                3684702
                23239116
                86af6718-a3bd-45cf-9c60-46fb0b5ee98c
                © Springer-Verlag Berlin Heidelberg 2012
                History
                : 12 June 2012
                : 14 November 2012
                Categories
                Review
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2013

                Orthopedics
                exercise,physical activity,cachexia,muscle wasting,cancer,resistance training,aerobic training,inflammation

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