Mechanisms of growth impairment in pediatric Crohn's disease.

Crohn's disease manifests during childhood or adolescence in up to 25% of patients. The potential for linear growth impairment as a complication of chronic intestinal inflammation is unique to pediatric patient populations. Insulin-like growth factor I (IGF-I), produced by the liver in response to growth hormone (GH) stimulation, is the key mediator of GH effects at the growth plate of bones. An association between impaired growth in children with Crohn's disease and low IGF-I levels is well recognized. Early studies emphasized the role of malnutrition in suppression of IGF-I production. However, a simple nutritional hypothesis fails to explain all the observations related to growth in children with Crohn's disease. The direct, growth-inhibitory effects of proinflammatory cytokines are increasingly recognized and explored. The potential role of noncytokine factors, such as lipopolysaccharides, and their potential to negatively influence the growth axis have recently been investigated with intriguing results. There is now reason for optimism that the modern anticytokine therapeutic agents available for treating children and adolescents with Crohn's disease will reduce the prevalence of this otherwise common complication. As our understanding of the mechanisms that underlie growth impairment advance, so too should the opportunity for developing further novel and targeted therapies.