ENTERAL VS IV FEEDING--EFFECT ON MUCOSAL IMMUNITY

描述(摘自申请者的摘要)：廉价疗法 它们可以大大减少危重病人的败血症并发症 影响到美国每年在这些并发症上花费的50-100亿美元。 肠内喂养显著降低肺炎并发症 静脉(IV-TPN)喂养通过未知的防御机制。数据 来自我们实验室的证据表明，IV-TPN或元素饮食(ED) 通过肠道相关淋巴萎缩损害粘膜免疫 小鼠组织(GALT)与其主要效应臂--IgA的降低 粘膜免疫。呼吸道中依赖免疫球蛋白的抗病毒防御 任何形式的肠道喂养都能维持，但静脉注射会恶化 喂食。这项建议侧重于途径和营养类型的影响 给予肠道特有的营养物质(精氨酸和谷氨酰胺)，以及 不同神经肽对胃肠道和呼吸道免疫球蛋白A介导防御的影响 一条小路。在饮食控制下消耗高尔基体(IV或ED)或 GALT维持饮食(食物或复合肠道饮食)，免疫的小鼠将 在病毒(PR8)或细菌(Ps)模型中受到挑战铜绿假单胞菌和圣母菌。 肺炎)肺炎模型。具有正常GALT系统的免疫动物避免 致命性肺炎，无免疫力或无免疫能力者死亡。他们的 假说是饮食引起的高尔特萎缩会损害 通过呼吸道抵御严重的感染挑战 饮食、神经肽或药物引起的肠外黏膜防御功能低下 特殊的营养操作。将分析高尔特细胞中的变化 细胞因子的产生或免疫球蛋白A刺激的信息(IL-4、IL-5、IL-6和 转化生长因子-β)和免疫球蛋白A抑制(干扰素和肿瘤坏死因子-β)细胞因子。具体的 目的是：调查影响粘膜防御的因素；确定 营养和神经肽操作后防御系统的排列；以及 用临床适用的活体来挑战这些被操纵的防御 感染剂。主要的假设是饮食控制 损害高尔特也会损害正常的粘膜防御和饮食， 神经肽，或特殊的营养操作，使GALT正常化 使IgA介导的粘膜防御和GALT细胞因子环境正常化。

DESCRIPTION (Adapted from applicant's abstract): Inexpensive therapies which reduce septic complications of critically ill patients could greatly impact the $5-10 billion spent annually in the U.S. on these complications. Enteral feeding significantly reduces the complication of pneumonia compared with intravenous (IV-TPN) feeding through unknown defense mechanisms. Data from our laboratory demonstrates that IV-TPN or an elemental diet (ED) impairs mucosal immunity through atrophy of the gut-associated lymphoid tissue (GALT) in the mouse and reduction of IgA, the major effector arm of mucosal immunity. IgA-dependent antiviral defenses in the respiratory tract are maintained with any form of enteral feeding but deteriorate with IV feeding. This proposal focuses on the effect of route and type of nutrient administration, of gut-specific nutrients (arginine and glutamine), and various neuropeptides on IgA-mediated defenses in the GI and the respiratory tract. Following dietary manipulation with GALT-depleting (IV or ED) or GALT-maintaining diets (chow or complex enteral diet), immunized mice will be challenged in models of viral (PR8) or bacterial (Ps. aeruginosa and St. pneumoniae) pneumonia models. Immune animals with normal GALT systems avoid fatal pneumonitis while nonimmune or immunoincompetent die. Their hypothesis is that a diet-induced atrophy of the GALT impairs the ability of the respiratory tract to withstand a severe infectious challenge through depressed extraintestinal mucosal defenses after dietary, neuropeptide or specialty nutrient manipulation. GALT cells will be analyzed for changes in cytokine production or message of IgA stimulating (IL-4, IL-5, IL-6, and TGF-beta) and IgA-inhibiting (IFN and TNF-beta) cytokines. The specific aims are to: investigate factors influencing mucosal defenses; define permutations in defenses after nutrient and neuropeptide manipulations; and to challenge these manipulated defenses with clinically applicable in vivo infectious agents. The main hypothesis is that dietary manipulations which impair the GALT also impairs normal mucosal defenses and that dietary, neuropeptide, or specialty nutrient manipulations which normalize GALT also normalize IgA-mediated mucosal defense and the GALT cytokine milieu.