IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance.
Level 5 - mechanism / opinion, no new human data
Narrative review of biological mechanisms and genetic variants without systematic methodology or original human data
PubMed 36168944 · doi:10.1111/sms.14241
What was done
This narrative review synthesizes evidence on the dual signaling pathways of interleukin-6 (IL-6) during acute exercise and chronic training. It describes the divergent mechanisms of classical signaling (via cell-surface membrane-bound receptors) versus trans-signaling (via soluble IL-6 receptors), and details the clinical and functional impact of the IL-6R single nucleotide polymorphism (SNP) rs2228145 on health and exercise performance.
What was found
The abstract reports no quantitative values or statistical comparisons. It details that IL-6 release from skeletal muscle increases with exercise duration, intensity, and muscle glycogen depletion. Classical signaling is highlighted as the primary pathway active during exercise, supporting energy homeostasis and exerting anti-inflammatory actions. In contrast, trans-signaling involves soluble IL-6 receptors (sIL-6R), possesses a longer half-life, acts across broad cell types, and mediates pathological inflammation. The rs2228145 SNP elevates circulating sIL-6R levels, shifting pathway balance toward trans-signaling and linking to conditions including rheumatoid arthritis, type 1 diabetes, and severe COVID-19.
Why it matters
The review provides a mechanistic framework explaining how exercise-induced IL-6 promotes metabolic adaptation and anti-inflammatory outcomes rather than systemic inflammation, while identifying genetic variations that could modulate individual responses to training and disease risk.
Limits
The paper is a non-systematic narrative review providing qualitative biological models rather than primary empirical data. The abstract lacks quantitative effect sizes, pooled metrics, participant numbers, and search criteria. Clinical and performance outcomes remain theoretical extrapolations of pathway biology rather than directly measured prospective endpoints.
Cited by
- supports The post-exercise spike in IL-6 is particularly pronounced when skeletal muscle glycogen stores are depleted.