Paradoxical role of IL-6 in cancer

Interleukin-6 (IL-6) is a cytokine involved in immune responses, inflammation, and metabolism. It is produced by various cells, including immune cells, adipocytes, and muscle tissue (1). In the context of cancer, IL-6 can function both as a promoter and an inhibitor of tumor growth.

Skeletal muscle is a significant source of circulating IL-6 in individuals who participate in exercise training (2). Research has shown that engaging in 150–300 minutes of exercise weekly can reduce the risk of several cancers, such as breast, colon, endometrial, kidney, and liver cancers, as well as myeloma and non-Hodgkin’s lymphoma (3, 4).

Paradoxical role of IL-6 in cancer

A recent study published in Trends Endocrinol Metab (Orange ST et al., 2023) (6) investigates the complex role of IL-6 in cancer development and explores how physical activity influences this cytokine.

Highlights:

• IL-6 can either inhibit or promote cancer, depending on the specific context. 
• It is released from skeletal muscles during exercise and by immune cells at inflammation sites and within the tumor microenvironment.
• Muscle-derived IL-6 improves insulin sensitivity, boosts anti-inflammatory cytokines, enhances immune response, and may protect against cancer progression.
• Conversely, prolonged IL-6 signaling in inflammation and tumors can promote chronic inflammation and tumor growth.         

 

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Literature:

1. IL-6 Signaling in Immunopathology: From Basic Biology to Selective Therapeutic Intervention. Schumertl T, Lokau J, Garbers C. Immunotargets Ther. 2025 Jul 5;14:681-695. doi: 10.2147/ITT.S485684. PMID: 40636466; PMCID: PMC12239904.
2. Exercise as an anti-inflammatory therapy for cancer cachexia: a focus on interleukin-6 regulation. Daou HN. Am J Physiol Regul Integr Comp Physiol. 2020 Feb 1;318(2):R296-R310. doi: 10.1152/ajpregu.00147.2019. Epub 2019 Dec 11. PMID: 31823669.
3. Amount and Intensity of Leisure-Time Physical Activity and Lower Cancer Risk. Matthews CE, Moore SC, Arem H, Cook MB, Trabert B, Håkansson N, Larsson SC, Wolk A, Gapstur SM, Lynch BM, Milne RL, Freedman ND, Huang WY, Berrington de Gonzalez A, Kitahara CM, Linet MS, Shiroma EJ, Sandin S, Patel AV, Lee IM. J Clin Oncol. 2020 Mar 1;38(7):686-697. doi: 10.1200/JCO.19.02407. Epub 2019 Dec 26. PMID: 31877085; PMCID: PMC7048166.
4. The Impact of Exercise on Cancer Mortality, Recurrence, and Treatment-Related Adverse Effects. Cormie P, Zopf EM, Zhang X, Schmitz KH. Epidemiol Rev. 2017 Jan 1;39(1):71-92. doi: 10.1093/epirev/mxx007. PMID: 28453622.
5. American College of Sports Medicine Roundtable Report on Physical Activity, Sedentary Behavior, and Cancer Prevention and Control. Patel AV, Friedenreich CM, Moore SC, Hayes SC, Silver JK, Campbell KL, Winters-Stone K, Gerber LH, George SM, Fulton JE, Denlinger C, Morris GS, Hue T, Schmitz KH, Matthews CE.Med Sci Sports Exerc. 2019 Nov;51(11):2391-2402. doi: 10.1249/MSS.0000000000002117. PMID: 31626056; PMCID: PMC6814265.
6. The exercise IL-6 enigma in cancer. Orange ST, Leslie J, Ross M, Mann DA, Wackerhage H. Trends Endocrinol Metab. 2023 Nov;34(11):749-763. doi: 10.1016/j.tem.2023.08.001. Epub 2023 Aug 24. PMID: 37633799.