RESPONSE TO ANTI-TUMOR NECROSIS FACTOR-A ANTIBODY IN CHILDREN WITH CROHN'S

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。患有克罗恩病的儿童在最初诊断时往往营养不良。肿瘤坏死因子-a在克罗恩病中起关键作用，表现为血清肿瘤坏死因子-α水平、肠道肿瘤坏死因子-α信使核糖核酸水平和肠道肿瘤坏死因子-α分泌细胞增加。抗肿瘤坏死因子-a抗体(Infliximab)是诱导和维持克罗恩病临床缓解的有效方法。本研究的目的是量化克罗恩病儿童在抗肿瘤坏死因子-α抗体治疗前后蛋白质和脂肪代谢、静息能量消耗和白蛋白合成的变化。我们推测，这种治疗将减少蛋白质和脂肪的分解代谢，减少静息能量消耗，并增加白蛋白合成。我们的假设将通过在每个儿童计划接受抗肿瘤坏死因子-a抗体的早上，在禁食和静脉喂养状态下静脉注射标记氨基酸来检验。连续抽血可以分析蛋白质和白蛋白的代谢率。间接呼吸量热法将在研究的空腹和进食部分结束时进行，以分析静息能量消耗和脂质氧化。在访问期间，将对每个儿童进行儿童克罗恩病活动指数，包括症状的主观报告、体检结果和三项实验室检查(红细胞压积、血沉和血清白蛋白)。两周后，这些孩子将以同样的方式接受研究。

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. Children with Crohn's disease are often malnourished at their initial diagnosis. Tumor necrosis factor-a (TNF-a) plays a pivotal role in Crohn's disease, as evidenced by increased serum TNF-a levels, intestinal TNF-a mRNA levels, and intestinal TNF-a secreting cells. Anti-tumor necrosis factor-a (anti-TNF-a) antibody (Infliximab) is an effective therapy for the induction and maintenance of clinical remission of Crohn's disease. The aim of this study is to quantify changes in protein and lipid metabolism, resting energy expenditure, and albumin synthesis in children with Crohn's disease before and after treatment with anti-TNF-a antibody. We hypothesize that this treatment will decrease protein and lipid catabolism, decrease resting energy expenditure, and increase albumin synthesis. Our hypotheses will be tested by administering intravenous labeled amino acids in the fasting and intravenously fed states on the morning each child is scheduled to receive anti-TNF-a antibody. Serial blood draws will allow for analysis of rates of protein and albumin metabolism. Indirect respiratory calorimetry will be conducted at the end of the fasting and fed portions of the study for analysis of resting energy expenditure and lipid oxidation. The Pediatric Crohn's Disease Activity Index, including subjective report of symptoms, physical examination findings, and three laboratory examinations (hematocrit, erythrocyte sedimentation rate, and serum albumin), will be administered to each child during the visit. These children will then be studied in an identical manner two weeks later.