METABOLIC RESPONSE TO INFLIXIMAB IN PEDIATRIC ULCERATIVE COLITIS

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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 ulcerative colitis 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 steroid-resistant ulcerative colitis. The objective of this application is to characterize protein and energy metabolism and their response to anti-TNF- therapy in children with active ulcerative colitis in both the fasting and parenterally fed states. The central hypothesis of this application is that inflammatory cytokines present in ulcerative colitis, including TNF- , increase net protein catabolism and resting energy expenditure and that anti-TNF- therapy will result in improvement in these metabolic measurements. Our long-range goal is to optimize the nutritional and growth outcomes of children with ulcerative colitis. Children with steroid-resistant ulcerative colitis who have been scheduled for their initial dose of infliximab will be recruited for this study. To accomplish the objectives of our aims, these children will be studied just prior to and two weeks following their initial dose of infliximab. Using stable isotope techniques, we will measure protein kinetics and balance during both the fasting state and parenteral nutrition infusion. Using indirect calorimetry, resting energy expenditure will be determined during fasting and parenteral nutrition infusion. The proposed work is innovative, because it expands our knowledge of the utilization of nutrition in ulcerative colitis. It is our expectation that this approach will more clearly delineate the underlying causes of growth disturbance in children with ulcerative colitis.