PROTEIN AND ENERGY METABOLISM IN PEDIATRIC CROHN'S DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Acute exacerbations of Crohn's disease lead to negative energy and protein balances, which may contribute to malnutrition, growth retardation and poor healing. Infliximab, an anti-tumor necrosis factor (TNF)- antibody, has been efficacious in children with Crohn's disease. The objective of this application is to characterize the systemic utilization of nutrition and its response to corticosteroid and anti-TNF- therapies in these children in both the fasting and fed states. The central hypothesis of this application is that inflammatory cytokines present in Crohn's disease, including TNF- , increase net protein catabolism and energy expenditure, and that anti-TNF- therapy will result in a greater improvement in these metabolic measurements than traditional corticosteroid therapy. Our long-range goal is to optimize the nutritional and growth outcomes of children with Crohn's disease. Children with recurrent Crohn's disease who have been scheduled for either infliximab or corticosteroid therapy will be recruited for this study. To accomplish the objectives of our aims, these children will be studied just prior to, and two and fourteen weeks following their initial dose of infliximab or beginning of corticosteroid therapy. Using stable isotope techniques, we will measure protein kinetics and balance during both the fasting state and enteral nutrition infusion. Using indirect calorimetry, resting energy expenditure will be determined during fasting and enteral nutrition infusion. The proposed work is innovative, because it expands our knowledge of the utilization of nutrition in Crohn's disease. It is our expectation that this approach will more clearly delineate the underlying causes of growth disturbance in children with Crohn's disease.