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Immuno-modulatory Effects of Parenteral Nutrition After Intestinal Failure

肠衰竭后肠外营养的免疫调节作用

基本信息

批准号：
7282651
负责人：
STEPHEN H BENEDICT
金额：
$ 13.94万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7282651
关键词：
Acute-Phase Reaction Agreement Animal Model Animals Antibodies Antigens Applications Grants Arachidonic Acids Attenuated Biological Assay Blood specimen CD Antigens CD28 Antigens CD28 gene CD3 Antigens CD4/CD8 ratio procedure CD8B1 gene Catheters Cell Adhesion Molecules Cell Count Cell division Chronic Chronic stress Clinical Clinical Trials Competence Condition Coupled Cytokine Receptors Data Depth Development Dinoprostone Disease Drug Formulations Eicosanoids Enzyme-Linked Immunosorbent Assay Epitopes Esters Evaluation Event Exhibits Failure Family suidae Fatty Acids Flow Cytometry Foundations Functional disorder Goals Hemagglutination Home environment Human Immune Immune Sera Immune System Diseases Immune response Immunization Impairment Individual Infection Inflammation Inflammatory Intercellular adhesion molecule 1 Interleukin 6 Receptor Interleukin-2 Interleukin-4 Interleukin-6 Intestines Intramuscular Injections Ionomycin Label Lead Lipids Liver diseases Longitudinal Studies Lymphocyte Lymphocyte Function Measurement Mediating Mediator of activation protein Membrane Memory Mental Depression Metabolic Bone Diseases Mitogens Modeling Modification Monoclonal Antibodies Mus Myristates NIH Program Announcements Natural History Nature Newborn Infant Numbers Nutrition Therapy Parenteral Nutrition Pathogenesis Patients Phorbol Phorbols Phytohemagglutinins Population Positioning Attribute Process Prostaglandins E Proteins Protocols documentation Publishing Rattus Reporting Research Research Personnel Risk Septicemia Serum Short Bowel Syndrome Small Intestines Standards of Weights and Measures Stress Sus scrofa T memory cell T-Cell Activation T-Cell Receptor T-Lymphocyte TNF gene TNFR-Fc fusion protein Testing Time Study Transplantation Treatment Effectiveness Tumor Necrosis Factor-alpha Tumor Necrosis Factors United States Urine Vaccine Antigen Vaccines Venous Viral Hemagglutinins Viral Proteins Virion Weaning Week Western Blotting Work analog base carboxyfluorescein clinically significant cohort cysteine rich protein cytokine cytotoxic design healthy aging human MPP1 protein human TNF protein immune function indexing influenza virus vaccine influenzavirus innovation myristate novel therapeutics peripheral blood receptor response

项目摘要

DESCRIPTION (provided by applicant): Individuals with intestinal failure require long-term parenteral nutrition (LTPN) therapy for survival. LTPN patients are at risk for parenteral nutrition (PN)-associated liver disease, central venous catheter-related septicemia and metabolic bone disease. These conditions suggest LTPN use is associated with chronic inflammatory sequelae and a potential for associated immune dysfunction. While PN animal models support this contention, there are no clinical investigations that have systematically examined the relationship between PN and immune and inflammatory mediators in a stable group of LTPN patients. We hypothesize that LTPN is associated with a cytokine mediated inflammatory process that influences T cell activity and impairs subsequent cellular and humoral defenses. Our long-term goal is elucidation of LTPN-associated events responsible for inflammation and immune dysfunction to allow development of novel therapeutic approaches to attenuate LTPN associated complications. The aims of this R21 proposal are: (Aim 1) To establish whether LTPN patients exhibit a chronic state of inflammation that results in abnormal modulation of cytokines, cytokine receptors and accessory membrane molecules related to immune stress. (Aim 2) To establish whether LTPN patients exhibit altered numbers and responses of T cells through (a) enumeration of (1) T cells, (2) helper and cytotoxic subsets and ratios, (3) the percentage of naive T cells versus effector and memory T cells and (4) the percentage of CD3+CD28(-) T cells and (b) assessment of T cell proliferative responses by mitogen stimulation and co-stimulation through the T cell antigen receptor (CDS) and CD28. (Aim 3) To determine whether LTPN patients exhibit a reduced humoral immune response against Influenza virus vaccine. This study will provide the first comprehensive assessment of stable LTPN patients' inflammatory and immune status. The data obtained will position the research team to develop more mechanistically in-depth RO1 proposals that investigate human patients and a murine PN animal model.

描述（由申请人提供）：肠衰竭患者需要长期肠外营养（LTPN）治疗以维持生存。LTPN患者存在肠外营养（PN）相关肝病、中心静脉导管相关败血症和代谢性骨病的风险。这些情况表明LTPN的使用与慢性炎症后遗症和潜在的相关免疫功能障碍有关。虽然PN动物模型支持这一观点，但在一组稳定的LTPN患者中，没有临床研究系统地检查PN与免疫和炎症介质之间的关系。我们假设LTPN与细胞因子介导的炎症过程有关，炎症过程影响T细胞活性并损害随后的细胞和体液防御。我们的长期目标是阐明导致炎症和免疫功能障碍的LTPN相关事件，从而开发新的治疗方法来减轻LTPN相关并发症。本R21提案的目的是：（目的1）确定LTPN患者是否表现出慢性炎症状态，导致与免疫应激相关的细胞因子、细胞因子受体和辅助膜分子的异常调节。（目的2）通过(a)列举(1)T细胞，(2)辅助和细胞毒性亚群和比率，(3)初始T细胞与效应T细胞和记忆T细胞的百分比，(4)CD3+CD28(-) T细胞的百分比，以及(b)通过T细胞抗原受体（CDS）和CD28刺激丝裂原和共刺激T细胞来评估T细胞增殖反应，来确定LTPN患者是否表现出T细胞数量和反应的改变。（目的3）确定LTPN患者对流感病毒疫苗的体液免疫反应是否降低。本研究将首次全面评估稳定LTPN患者的炎症和免疫状态。获得的数据将使研究团队能够制定更深入的机械RO1建议，以调查人类患者和小鼠PN动物模型。