The Role of IL-6 and Myogenic Transcription Factors in Skeletal Muscle Wasting and Dysfunction Due to Cancer Cachexia

Abstract

Cardiac Ultrasound Laboratory, Department of Cardiology, Massachusetts General Hospital, Boston, USACancer cachexia is a complex syndrome of progressive weight loss and anorexia which contributes significantly to themorbidity and mortality of cancer patients. The causes contributing to the progression of this debilitating syndrome arelikely to be multi-factorial and diagnosis is frequently made late into the disease process at the pre-terminal stage;even though it may be present in the early stages of tumor growth before any overt signs or symptoms of malignancy.Weight loss and the associated symptoms are a significant component of this syndrome and are largely secondary tothe impairment of function, loss of mass and breakdown of skeletal muscle. There is now emerging evidence for a role ofpro-inflammatory cytokines such as IL-6 and TNF in the pathophysiology of this disease. Genetic and molecular studiesare also beginning to reveal some of the molecules affected in this disease process. This review discusses the role ofIL-6 signalling and the evidence linking its effects on molecular pathways underpinning this pathophysiological processat a cellular level.