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The exercise IL-6 enigma in cancer

2023/08/24 by Samuel T. Orange, Jack Leslie, Mark Ross +2 · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Adipokines, Inflammation, and Metabolic Diseases #Exercise and Physiological Responses #Inflammasome and immune disorders

paper · pdf · doi:10.1016/j.tem.2023.08.001

openalex publication_date 2023/08/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

Interleukin (IL)-6 elicits both anticancer and procancer effects depending on the context, which we have termed the 'exercise IL-6 enigma'. IL-6 is released from skeletal muscles during exercise to regulate short-term energy availability. Exercise-induced IL-6 provokes biological effects that may protect against cancer by improving insulin sensitivity, stimulating the production of anti-inflammatory cytokines, mobilising immune cells, and reducing DNA damage in early malignant cells. By contrast, IL-6 continuously produced by leukocytes in inflammatory sites drives tumorigenesis by promoting chronic inflammation and activating tumour-promoting signalling pathways. How can a molecule have such opposing effects on cancer? Here, we review the roles of IL-6 in chronic inflammation, tumorigenesis, and exercise-associated cancer prevention and define the factors that underpin the exercise IL-6 enigma.

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