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PubMed· 2026· Review

Interleukin-6 in acute exercise and training: what is the biological relevance?

Christian P. Fischer

Short summary

Contracting skeletal muscles are the primary source of the significant increase in Interleukin-6 (IL-6) observed during prolonged, intense exercise, influencing immune and metabolic responses.

AI-generated from the title and abstract; the full text is not read.

Key points

  • Skeletal muscle is the dominant source of exercise-induced IL-6.
  • Exercise intensity and duration, not mode, dictate IL-6 response magnitude.
  • Muscle contraction triggers IL-6 synthesis via calcium, glucose, and ROS pathways.
  • IL-6 influences metabolic and immune systems during exercise.
  • Exercise training reduces both basal and exercise-induced IL-6 levels.

AI-generated from the title and abstract; the full text is not read.

Abstract

It is now recognized that contracting skeletal muscle may synthesize and release interleukin-6 (IL-6) into the interstitium as well as into the systemic circulation in response to a bout of exercise. Although several sources of IL-6 have been demonstrated, contracting muscles contributes to most of the IL-6 present in the circulation in response to exercise. The magnitude of the exercise-induced IL-6 response is dependent on intensity and especially duration of the exercise, while the mode of exercise has little effect. Several mechanisms may link muscle contractions to IL-6 synthesis: Changes in calcium homeostasis, impaired glucose availability, and increased formation of reactive oxygen species (ROS) are all capable of activating transcription factors known to regulate IL-6 synthesis. Via its effects on liver, adipose tissue, hypothalamic-pituitary-adrenal (HPA) axis and leukocytes, IL-6 may modulate the immunological and metabolic response to exercise. However, prolonged exercise involving a significant muscle mass in the contractile activity is necessary in order to produce a marked systemic IL-6 response. Furthermore, exercise training may reduce basal IL-6 production as well as the magnitude of the acute exercise IL-6 response by counteracting several potential stimuli of IL-6. Accordingly, a decreased plasma IL-6 concentration at rest as well as in response to exercise appears to characterize normal training adaptation.

The authors' abstract, as published at the source. PubMed, 2026 · DOI ↗

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Field: Rehabilitation

RehabilitationMedicine