ENTERAL VS IV FEEDING--EFFECT ON MUCOSAL IMMUNITY

描述（改编自申请人摘要）：廉价疗法 减少重症患者的脓毒性并发症， 美国每年花费在这些并发症上的50 - 100亿美元。 肠内喂养显著减少肺炎并发症， 静脉（IV-TPN）喂养通过未知的防御机制。 数据 我们实验室的研究表明，IV-TPN或元素饮食（艾德） 通过肠道相关淋巴萎缩损害粘膜免疫 组织（GALT）在小鼠和减少伊加，主要效应臂的 粘膜免疫 呼吸道中IgA依赖性抗病毒防御 任何形式的肠内喂养都能维持，但静脉注射会恶化 喂食 该建议侧重于营养素途径和类型的影响 肠特异性营养素（精氨酸和谷氨酰胺）的施用，以及 各种神经肽对IgA介导的胃肠道和呼吸道防御的影响 道。 在饮食控制和GALT消耗（IV或艾德）后，或 GALT维持饮食（食物或复合肠内饮食），免疫小鼠将 在病毒（PR 8）或细菌（Ps. aeruginosa和St. 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，而非免疫或免疫功能不全死亡。 他们的 一种假说是饮食诱导的GALT萎缩损害了 呼吸道抵御严重的感染性挑战， 饮食、神经肽或 专业营养调控 将分析GALT细胞的变化， 伊加刺激的细胞因子产生或信息（IL-4、IL-5、IL-6和 TGF-β）和IgA抑制（IFN和TNF-β）细胞因子。 具体 目的是：调查影响粘膜防御的因素;定义 营养素和神经肽操纵后的防御排列;以及 用临床上适用的体内试验来挑战这些被操纵的防御 传染源 主要的假设是， 损害GALT也损害正常的粘膜防御， 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.