PATHOBIOLOGY OF INTRAVENOUS LIPID EMULSIONS IN CHILDREN

静脉脂肪乳剂是全胃肠外营养的重要组成部分 营养(TPN)。脂肪乳剂的TPN并发症可见， 然而，并包括发烧和“热原反应”，肺异常 功能，和血小板减少。我们的临床印象是 血小板减少是脂肪乳剂治疗的一个特殊问题 新生儿和烧伤儿童。我们认为C反应蛋白 (CRP)，存在于正常血浆中的痕量，但显著升高 感染、炎症或创伤，与磷胆碱结合 一种脂肪乳剂的乳化剂，用于制备能够活化的脂质体 补体，产生过敏性毒素C3a和C5a，从而聚集 和引起发烧的血小板。 在临床研究中，我们将确定血小板减少症的发生率和 新生儿和烧伤儿童服用脂质的其他不良反应 乳剂疗法，并试图将这些反应与C反应蛋白相关联， 过敏性毒素水平，以及我们发现的定量血浆“乳膏”反应 已经发展起来了。我们还将研究一小部分成人患者，从 可以提取更大数量的顺序样本。 我们会用柱层析法纯化CRP，给我们足够的量 C反应蛋白用于体外实验。体外实验旨在 脂肪乳剂对鼻咽癌两种靶细胞的影响 反应，巨噬细胞和血小板。我们将研究详细的说明。 单核细胞经不同类型的脂类孵育后对IL-1的影响 血浆。正常血浆，补充不同浓度的 C反应蛋白，各种补体缺乏血浆将被用来研究 C-反应蛋白和补体的相对贡献 内源性热原，IL-1。 我们将研究通过脂质-血浆相互作用激活血小板。补充物 将使用空腹血浆和F(ab‘)抗-CRP来确定 血小板活化包括脂质体-C反应蛋白结合、C3a生成、或 脂质体-CRP-Clq结合，或某种组合。 最后，我们将尝试进一步研究兔的病理事件。 在正常和升高的CRP水平均注入脂肪乳剂的情况下， 确定C反应蛋白和补体激活在这些过程中的作用 反应(发热、中性粒细胞减少、血小板减少)。

Intravenous lipid emulsions are an important part of total parenteral nutrition (TPN). Complications of TPN with lipid emulsions are seen, however, and include fever and "pyrogen reactions," abnormal pulmonary function, and thrombocytopenia. It had been our clinical impression that thrombocytopenia is a particular problem of lipid emulsion therapy in some neonates and children with burns. We believe that C-reactive protein (CRP), present in trace amounts in normal plasma but markedly elevated with infection, inflammation, or trauma, combines with the phosphocholine emulsifier of lipid emulsion to create liposomes capable of activating complement, generating anaphylatoxins C3a and C5a, thereby aggregating platelets and causing fever. In clinical studies, we will define the incidence of thrombocytopenia and other adverse reactions in neonates and burned children receiving lipid emulsion therapy, and attempt to correlate these reactions with CRP, anaphylatoxin levels, and a quantitative plasma "creaming" reaction that we have developed. We will also study a small number of adult patients, from whom a larger number of sequential samples can be drawn. We will purify CRP by column chromatography to give us adequate amounts of CRP for in vitro experimentation. In vitro experiments are designed to study the effects of lipid emulsion on two target cells of adverse reactions, the macrophage and the platelets. We will study the elaboraton of IL-1 by monocytes challenged with lipid incubated in different types of plasma. Normal plasma, plasma supplemented with varying concentraions of CRP, various complement deficient plasmas will be used to study the relative contributions of CRP and complement in the elaboration of the endogenous pyrogen, Il-1. We will study platelet activation by lipid-plasma interactions. Complement deficient plasma and F (ab') anti-CRP will be used to determine whether platelet activation involves liposome-CRP binding, C3a generation, or liposome-CRP-Clq binding, or some combination. Finally, we will attempt to further study the pathologic events in rabbits with both normal and elevated CRP levels infused with lipid emulsion, to determine the role of CRP and of complement activation in producing these reactions (fever, neutropenia, thrombocytopenia).