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1、1Immune modulation by parenteral lipid emulsions作者：Geert JA Wanten and Philip C Calder,【摘要 】 Total parenteral nutrition is the final option for nutritional support of patients with severe intestinal failure. Lipid emulsions constitute the main source of fuel calories and fatty acids (FAs) in parente
2、ral nutrition formulations. However, adverse effects on patient outcomes have been attributed to the use of lipids, mostly in relation to impaired immune defenses and altered inflammatory responses. Over the years, this issue has remained in the limelight, also because technical advances have provid
3、ed no safeguard against the most daunting problems, ie, infectious complications. Nevertheless, numerous investigations have failed to produce a clear picture of the immunologic characteristics of the most commonly used soybean oilCderived lipid emulsions, although their high content of nC6 polyunsa
4、turated FAs (PUFAs) has been considered a drawback because of their proinflammatory potential. This 2concern initiated the development of emulsions in which part of the nC6 FA component is replaced by less bioactive FAs, such as coconut oil (rich in medium-chain saturated FAs) or olive oil (rich in
5、the nC9 monounsaturated FA oleic acid). Another approach has been to use fish oil (rich in nC3 PUFA), the FAs of which have biological activities different from those of nC6 PUFAs. Recent studies on the modulation of host defenses and inflammation by fish-oil emulsions have yielded consistent data,
6、which indicate that these emulsions may provide a tool to beneficially alter the course of immune-mediated conditions. Although most of these lipids have not yet become available on the US market, this review synthesizes available information on immunologic characteristics of the different lipids th
7、at currently can be applied via parenteral nutrition support. 【关键词】 total parenteral nutrition lipid emulsion immunology inflammation fatty acids eicosanoidsINTRODUCTION3Over the past 4 decades, parenteral nutrition has proven itself to be the therapeutic strategy of choice for nutritional support o
8、f patients with severe chronic intestinal failure (1). Total parenteral nutrition (TPN) implies that all macronutrient (carbohydrates, amino acids, and lipids) and micronutrient (electrolytes, vitamins, and trace elements) requirements are met by means of an all-in-one sterile, aqueous solution that
9、 is administered into a large-bore central vein (2). Although nontunneled catheters positioned in the subclavian or jugular veins can be used for short-term TPN delivery in hospitalized patients, long-term TPN administration in the home setting requires the presence of a tunneled catheter, a subcuta
10、neous port, or an arteriovenous shunt to provide a site for venous access (3). Although the relevance of TPN support for clinical practice is beyond doubt, its high rate of complications remains a drawback (4). The nature, magnitude, and suggested management of these complications have been addresse
11、d (1, 5). Although mechanical (catheter occlusion) and metabolic (disturbances of fluids and electrolytes, liver dysfunction, and bone disease) problems 4frequently occur, complications related to venous access and infection remain the major problems (4, 6). With respect to the latter, lipids in TPN
12、 formulations have long been under scrutiny because of their alleged detrimental effects on immune function. For instance, a meta-analysis in surgical and critically ill patients reported higher complication rates in patients receiving lipid-based TPN than in those receiving lipid-free formulations
13、(7). However, the overall clinical proof for such negative effects is rather weak (8). Also, novel lipids have recently been introduced in the clinical arena, which promise to modulate inflammatory responses in a favorable manner and to improve the outcomes of patients with immune-mediated condition
14、s. These notions provided the background for the present review, which provides an overview of and insights regarding the currently available data on immune modulation by parenteral lipids.HISTORICAL PERSPECTIVELipids, in the form of olive oil (OO) and milk, for example, 5have been administered intr
15、avenously to humans for therapeutic purposes since the 17th century (9). Numerous adverse events resulting from lipid use led to the notion that the administration of fat by this route invariably causes severe complications, including fat embolism. The demonstration of a strong link between the pres
16、ence of malnutrition and the development of postoperative mortality in the 1930s by Studley (10) was a strong impetus for the exploration of better ways to deliver adequate fuel calories to these patients. After much trial and error, Schuberth and Wretlind (11) eventually succeeded in developing a nontoxic lipid emulsion prepared from soybean oil (SO) (Intralipid; Fresenius-Kabi, Bad Homburg, Germany) that was introduced in 1961. Wretlinds system of lipid-based TPN found i
