METABOLIC RESPONSE TO INFLIXIMAB IN PEDIATRIC ULCERATIVE COLITIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。溃疡性结肠炎急性加重导致能量和蛋白质负平衡，这可能导致营养不良、生长迟缓和愈合不良。英夫利西单抗是一种抗肿瘤坏死因子（TNF）抗体，对类固醇耐药的溃疡性结肠炎儿童有效。本申请的目的是表征空腹和胃肠外进食状态下活动性溃疡性结肠炎儿童的蛋白质和能量代谢及其对抗TNF治疗的反应。本申请的中心假设是溃疡性结肠炎中存在的炎性细胞因子，包括TNF-α，增加净蛋白质代谢和静息能量消耗，并且抗TNF-α治疗将导致这些代谢测量的改善。我们的长期目标是优化溃疡性结肠炎儿童的营养和生长结果。本研究将招募已计划接受英夫利西单抗初始剂量的类固醇耐药溃疡性结肠炎儿童。为了实现我们的目标，这些儿童将在英夫利西单抗首次给药前和给药后两周进行研究。使用稳定同位素技术，我们将测量空腹状态和肠外营养输注期间的蛋白质动力学和平衡。采用间接热量测定法，测定空腹和肠外营养输注期间的静息能量消耗。这项工作是创新的，因为它扩大了我们对溃疡性结肠炎营养利用的认识。我们期望这种方法能更清楚地描述溃疡性结肠炎儿童生长障碍的根本原因。

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.