The exercise IL-6 enigma in cancer

Trends Endocrinol Metab. 2023 Nov;34(11):749-763. doi: 10.1016/j.tem.2023.08.001. Epub 2023 Aug 24.

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.

Keywords: cancer; exercise; inflammation; interleukin-6; muscle.

Publication types

  • Review

MeSH terms

  • Carcinogenesis / metabolism
  • Cytokines / metabolism
  • Exercise / physiology
  • Humans
  • Inflammation / metabolism
  • Interleukin-6* / metabolism
  • Muscle, Skeletal / metabolism
  • Neoplasms* / metabolism

Substances

  • Cytokines
  • Interleukin-6
  • IL6 protein, human