Exercise as an anti-inflammatory therapy for cancer cachexia: a focus on interleukin-6 regulation

Cancer cachexia is a complicated disorder of extreme, progressive skeletal muscle wasting. It is directed by metabolic alterations and systemic inflammation dysregulation. Numerous studies have demonstrated that increased systemic inflammation promotes this type of cachexia and have suggested that cytokines are implicated in the skeletal muscle loss. Exercise is firmly established as an anti-inflammatory therapy that can attenuate or even reverse the process of muscle wasting in cancer cachexia. The interleukin IL-6 is generally considered to be a key player in the development of the microenvironment of malignancy; it promotes tumor growth and metastasis by acting as a bridge between chronic inflammation and cancerous tissue and it also induces skeletal muscle atrophy and protein breakdown. Paradoxically, a beneficial role for IL-6 has also been identified recently, and that is its status as a "founding member" of the myokine class of proteins. Skeletal muscle is an important source of circulating IL-6 in people who participate in exercise training. IL-6 acts as an anti-inflammatory myokine by inhibiting TNFα and improving glucose uptake through the stimulation of AMPK signaling. This review discusses the action of IL-6 in skeletal muscle tissue dysfunction and the role of IL-6 as an "exercise factor" that modulates the immune system. This review also sheds light on the main considerations related to the treatment of muscle wasting in cancer cachexia.