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

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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. 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.