The exercise IL-6 enigma in cancer

Samuel T. Orange, Jack Leslie, Mark Ross, Derek A. Mann, Henning Wackerhage

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


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.

Original languageEnglish
Pages (from-to)749-763
Number of pages15
JournalTrends in Endocrinology and Metabolism
Issue number11
StatePublished - Nov 2023


  • cancer
  • exercise
  • inflammation
  • interleukin-6
  • muscle


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