Stress-induced IL-6 regulation in pediatric bone growth disorders: current insights and therapeutic strategies

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Stress-induced upregulation of interleukin-6 (IL-6) signaling and its downstream pathophysiological consequences have garnered considerable attention in recent years. However, no comprehensive review has specifically examined the association between stress-induced IL-6 and its implications for bone health in children. During childhood, linear growth and peak bone mass acquisition are tightly regulated processes. Hence, this review aims to investigate current evidence on stress-induced IL-6 upregulation and its detrimental effects on pediatric bone health. Findings from animal models, knockout studies, pediatric inflammatory disorders, including juvenile idiopathic arthritis, pediatric systemic lupus erythematosus and inflammatory bowel disease, and models of metabolic stress collectively demonstrate that stress triggers IL-6, thereby impairing skeletal growth and increasing fragility. Data shows that persistent IL-6 upregulation not only disrupts the normal functioning of growth hormone, insulin-like growth factor-1 (GH/IGF-1) axis, enhances receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis, and promotes bone marrow adiposity. Further, stress-induced high levels of IL-6 adversely affect the skeletal, immune, and endocrine systems, thereby compromising skeletal development and bone growth in children. Elevated systemic or local IL-6 levels m

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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