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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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 研究中心，而研究中心不一定是研究者所在的机构。 克罗恩病患儿在最初诊断时往往营养不良。 肿瘤坏死因子-α（TNF-α）在克罗恩病中起关键作用，如通过增加的血清TNF-α水平、肠TNF-α mRNA水平和肠TNF-α分泌细胞所证明的。 抗肿瘤坏死因子-α（抗TNF-α）抗体（英夫利昔单抗）是诱导和维持克罗恩病临床缓解的有效疗法。 本研究的目的是量化克罗恩病儿童在抗TNF-a抗体治疗前后蛋白质和脂质代谢、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质代谢，减少静息能量消耗，并增加白蛋白的合成。 我们的假设将通过在每个儿童预定接受抗TNF-α抗体的早晨在禁食和静脉内进食状态下静脉内施用标记的氨基酸来检验。 连续抽血将允许分析蛋白质和白蛋白代谢率。 将在研究的空腹和进食部分结束时进行间接呼吸量热法，以分析静息能量消耗和脂质氧化。 在访视期间，将对每名儿童进行儿童克罗恩病活动指数，包括症状的主观报告、体格检查结果和三项实验室检查（红细胞压积、红细胞沉降率和血清白蛋白）。 两周后，将以同样的方式对这些儿童进行研究。

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, erythocyte 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.