A Critical Review on Mechanistic Cross Talk between Paediatric Inflammation and GH-IGF-1 Axis in Childhood Growth

Abstract

Linear growth during childhood is governed by the coordinated action of the growth hormone–insulin-like growth factor-1 (GH–IGF-1) axis, yet this endocrine system does not operate in isolation from the immune system. Chronic and acute inflammatory states, whether triggered by autoimmune disease, gastrointestinal disease, malnutrition, or gut mucosal dysfunction, exert profound and multi-level effects on somatic growth. This review synthesises current evidence on the bidirectional relationship between immune activation and the GH–IGF-1 axis in children, addressing mechanisms of hepatic growth hormone resistance, cytokine-mediated disruption of insulin-like growth factor binding proteins, direct cytokine action on growth plate chondrocytes, and the emerging role of the gut microbiome as an intermediary between mucosal immunity and somatotropic signalling. Clinical correlates are examined across juvenile idiopathic arthritis, inflammatory bowel disease, cystic fibrosis, coeliac disease and environmental enteric dysfunction, alongside evidence from anti-cytokine and recombinant growth hormone interventions that partially restore growth velocity. The review highlights substantial heterogeneity across paediatric populations, disease states and treatment protocols, and identifies persistent gaps regarding the long-term auxological outcomes of biologic therapy, the mechanistic contribution of gut microbial signalling, and the translational potential of anti-inflammatory strategies as adjuncts to conventional growth-promoting treatment. Addressing these gaps will be essential to optimise final adult height in children affected by chronic inflammatory disease.