Stress-induced IL-6 upregulation impairs skeletal growth and bone health in children with inflammatory diseases

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Frontiers in Medicine Published June 6, 2026 Medically reviewed June 6, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider stress-induced IL-6 as a potential mediator of bone growth impairment in pediatric inflammatory diseases, though evidence is largely preclinical.

This narrative review examines the role of stress-induced IL-6 upregulation in disrupting skeletal development and bone health in children with juvenile idiopathic arthritis, pediatric systemic lupus erythematosus, and inflammatory bowel disease. Drawing on findings from animal models, knockout studies, and clinical observations, the authors synthesize evidence that IL-6 upregulation impairs skeletal growth, increases bone fragility, disrupts GH/IGF-1 axis functioning, enhances osteoclastogenesis, promotes bone marrow adiposity, impairs stem cell differentiation, inhibits growth plate chondrocyte proliferation and maturation, restricts longitudinal bone growth, and impairs muscle health. All outcomes are reported qualitatively without effect sizes or confidence intervals. The review does not report specific study populations, sample sizes, comparators, or follow-up durations. The authors do not list explicit limitations but note the need for integrative therapeutic strategies that target both inflammation and redox imbalance. Given the reliance on animal and mechanistic data, clinicians should interpret these findings as hypothesis-generating rather than definitive. The review underscores the potential importance of managing stress and inflammation to preserve bone health in pediatric inflammatory conditions, but direct evidence from interventional trials in children is lacking.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

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 may exert direct deleterious effects on bone by impairing stem cell differentiation and inhibiting the proliferation and maturation of growth plate chondrocytes, ultimately restricting longitudinal bone growth. Moreover, elevated IL-6 levels may also impair muscle health and crosstalk between muscle and bone, thereby compromising skeletal integrity. Collectively, these findings underscore the need for integrative therapeutic strategies that target inflammation and redox imbalance in bone and other tissues, particularly in children. Better understanding stress-induced IL-6 dysregulation is critical for pediatric bone development and long-term skeletal health.