The Effects of a Short-Term Long-Chain-Triglyceride Infusion on the Postoperative Immune Function of Pediatric Patients Receiving a Gastrointestinal Surgical Procedure

By Li, Xiaogang Ying, Jiaoqian; Zeng, Shan; Li, Yixiong; Yang, Huixiang; Shen, Liangfang; Han, Jie; Chen, Jia; Shen, Hong

ABSTRACT. Objective: This clinical trial investigates whether short-term administration of long chain triglycerides (LCT) has any influence on the immune function in children following gastrointestinal surgery. Methods: Sixty pediatric patients receiving a gastrointestinal operation were randomly divided into the experimental group (n = 36) and the control group (n = 24). After abdominal operation, the subjects received parenteral nutrition (PN) support with or without LCT for 5 days. The patients’ fasting blood samples were respectively collected at 24 hours preoperative, then 24 hours and 120 hours postoperative. Blood parameters related to the patients’ immune function were measured. Results: Before surgery and LCT treatment, the experimental group and control group did not differ significantly in overall state of health. Except for a small increase of serum IgM at 24 hours postsurgery (p < .05), all parameters representing the patients' immune function showed no significant difference between the LCT group and the control group with respect to peripheral blood mononuclear cell (PBMC), T lymphocyte, CD4, CD8, CD4/CD8, serum immunoglobulin A (IgA), IgG, IgM, complement C3, C4, interleukin (IL)-2, IL-4, IL-10, IL-12, tumor necrosis factor (TNF)-alpha and IFN-gamma (p > .05, respectively) before the operation, 24 hours and 120 hours after the operation. Conclusions: A short-term LCT administration at an appropriate dosage and infusion speed does not alter the pediatric patients’ immune function after gastrointestinal surgery. The etiology and clinical significance of the slightly increased IgM 24 hours postsurgery need to be further investigated. (Journal of Parenteral and Enteral Nutrition 32:72-77, 2008) Parenteral nutrition (PN) can play a critical role in patient management. In clinical practice, it is indicated for patients who are unable to take oral or enteral nutrition, especially for pediatric patients receiving gastrointestinal surgery. Lipid emulsions included in PN are necessary for the provision of essential fatty acids (ie, linoleic acid and linolenic acid),1 and are extensively used as standard IV calorie-dense nutrients. In the absence of essential fatty acids, complications may develop in surgical patients, including delayed wound healing, increased infection susceptibility, and platelet dysfunction.2 omega-6 Fatty- acid-rich long-chain-triglyceride (LCT) emulsions, which contain fatty acid chains with 14, 16, 18, 20, and 22 carbon atoms and with double bonds, have been used in clinical practice for decades and are still the most commonly used parenteral fat source.

Fatty acids in LCT are the main component of cell membranes, and are responsible for membrane structural integrity and the production of eicosanoids. Lipids are also major metabolic regulators and can modulate human immune response.3,4 LCT is suspected to significantly affect many biochemical and physiologic functions related to inflammatory, immune, and protective reactions.4 There is evidence that surgical patients receiving LCT emulsions may be at risk of compromised immunity due to the inhibitory influence of LCT on human immune function, resulting in decreased resistance to infection.5,6 Concerns about the correlation between LCT and infectious morbidity were raised after a report of an increased risk of bacteremia related to the use of LCT in neonates.7 The suspected immunosuppressive effects of IV LCT infusion are a matter of great clinical concern and debate. However, most of the contradictory study results collected from in vitro experiments, in vivo rat models, limited cases of healthy volunteers or critically injured patients, or from clinical trials in subjects lacking normal immune function focus on the effects of long-term LCT application on immunity inhibition. There is little data on the influences of short- term postoperative LCT management on human immune function, especially for pediatric patients.

Some in vitro data suggest that chemotactic and random migration of leukocytes is decreased by LCT infusion8; mitogen-stimulated and interleukin (IL)-2-activated human lymphocyte proliferation are both inhibited in a dose-dependent manner by LCT emulsions.9 The decreased production of oxygen radicals by polymorphonuclear leukocytes caused by parenteral LCT may result in immunosuppression.10 LCT has also been reported to have an impact on mononuclear phagocytic function.11 However, in vivo results from the same report suggest that administration of a parenteral supply of LCT does not influence any of the investigated blood polymorphonuclear leukocytes (PMNL) function.11 In a rat model of Gram-negative bacteremia, PN with LCT increases bacterial growth in the liver and lungs, whereas the rat plasma levels of prostaglandin E2 (PGE^sub 2^) and mortality are unaffected.12 In Sprague-Dawley rats with trinitrobenzene sulfonic acid (TNB)-induced ileitis, LCT treatment did not seem to cause either morphological or function damage of polymorphonuclear neutrophils.13

Table I

Patient demographics before the surgery (n = 60)

Results are contradictory from clinical studies examining different patient populations investigating the suspected human immunity inhibition of LCT. Some researchers propose that the use of PN with LCT is not associated with human intestinal immune dysfunction.14 In an extensive clinical trial in patients undergoing bone marrow transplantation, who had an abnormal immune function, a moderate dose of LCT was found not to be associated with the incidence of bacterial or fungal infection.15 In a study of 10 malnourished patients with gastric cancer, LCT emulsions did not seem to affect monocyte function.16 On the contrary, a study of 8 normal subjects receiving LCT emulsions showed a significant increase in monocyte activity.17 It has been suggested that LCT infusions during the early postinjury period can increase susceptibility to infection, prolonged pulmonary failure, and delayed recovery in critically injured patients.18 A recent study of 11 healthy volunteers indicated that a single 500-mL dose of LCT emulsion may promote lymphocyte and neutrophil death, increasing susceptibility to infections.19 Fraser et al20 pointed out that LCT may block the reticuloendothelial system (RES) due to the absorption of LCT through the lymphatic system so as to interfere with the immune function of T cells and B cells, as well as promote damage to the phagocyte function. On the other hand, there is an argument that the administration of continuous LCT infusion does not impair 99Tc- sulfur colloid (TSC) clearance by the RES.21

The contradictory data from in vitro and in vivo experiments or from different clinical populations emphasize the necessity for additional trials. In surgical wards, PN with LCT is routinely administered to patients after gastrointestinal surgery. However, the influences of LCT on immune function of pediatric patients remain unclear and are clinically important. The purpose of this randomly controlled clinical trial is to investigate whether a short- term use of LCT in PN has any influence on immune function in pediatric patients undergoing gastrointestinal surgery.

MATERIALS AND METHODS

Sixty-eight pediatric patients undergoing gastrointestinal surgery in Xiangya Hospital and Hunan Provincial Children Hospital from February 2004 to December 2005 were enrolled in this study. All subjects were between the ages of 1 and 9 years, and did not take medications or dietary supplements. Patients were prospectively randomized to either the experimental LCT group or the control group. Each patient completed a medical history and a dietary evaluation to eliminate subjects with known inherited or chronic disease. The subjects underwent one of the following abdominal operations: radical macrosigmoid operation for Hirschsprung disease, pyloroplasty, or adhesiolysis for bowel obstruction. Patients with any of the following conditions were excluded: abnormal heart, lung, liver, or renal function; rheumatic fever; allergies or asthma; goiter; jaundice; metabolic diseases such as diabetes mellitus; taking hormone or any other medication affecting human immune function; blood transfusion; immunologically mediated disease or postoperative complications. Sixty-eight subjects were recruited to the study and 60 completed the trial. The mean age, gender, body weight, albumin, liver/renal function, category of diseases, and surgery did not differ among these 2 groups at study entry (p > .05; Table I). The study was approved by the research ethics committee of the Central South University of China. Informed consent was obtained from the parents or guardians of all patients.

A randomized design was used for patient grouping in this intention-to-treat study. The LCT-treated subjects (n = 36) received PN support for 5 days by continuous infusion via a peripheral-vein catheter at a dose of 418 kJ (100 kcal)/kg/d of nonprotein calories for the first 10 kg body weight, 209 kJ (50 kcal)/kg/d for the second 10 kg body weight, and 83.6 kJ (20 kcal)/kg/d for the third 10 kg body weight, 150:1 for the ratio of nonprotein calorie to nitrogen, 2:1 for the ratio of glucose to lipid.22 The PN mixed solution provided by the Preparation Center of PN Solutions of Xiangya Hospital included 20% Intralipid as the lipid source, 11.4% Novamin as the nitrogen source, Addamel N as the microelement source, and Soluvit N and Vitalipid N as the vitamin source. All the PN elements mentioned above were purchased from Sino-Sweden Pharmaceutical Corp Ltd (Wuxi, Jiangshu, China). As for the subjects in the control group without LCT administration (n = 24), they received the same routine IV transfusion that the LCT treatment subjects underwent, except that LCT was excluded from the PN mixed solution. The PN solutions prepared for the control patients contained the same amount of energy and dispensation ratio and the same amount of nitrogen, microelements, and vitamins as described above for the LCT-treated subjects. Insulin was administered at a dose of 1 unit/4 g glucose, as the patients’ blood glucose was higher than 6.1 mmol/L. The patients’ blood samples were collected into a serum-collecting tube at 24 hours preoperative, 24 hours, and 120 hours postoperative by venipuncture, according to the approved procedure for collection of diagnostic blood specimens. The number of neutrophil, peripheral blood mononuclear cell (PBMC), and lymphocyte percentage was counted by a hematology analyzer Sysmex XE2100 (TOA Medical Electronics, Kobe, Japan). T-lymphocyte subsets including CD4, CD8, and the ratio of CD4/CD8 were examined by a flow cytometer (FCM; BD Company, San Jose, CA), the monoclonal antibodies of CD4-FTTC and CD8-PE, against CD4 and CD8 receptors were purchased from Beckman-Coulter, Inc (Fullerton, CA). The blood samples were then allowed to clot (1 hour) at room temperature. The serum was separated by centrifugation at 500 x g for 10 minutes and was stored at -70[degrees]C. The serum concentrations of immunoglobulin A (IgA), IgG, IgM, and complement C3 and C4 were determined with the rate nephelometry assay by Array 360 System (Beckman-Coulter, Inc),23 using reagents obtained from Beckman. An in-house enzyme- linked immunosorbent assay (ELISA) was used to measure the cytokines’ concentrations in the serum, including interleukin (IL)- 2, IL-4, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma, according to the ELISA kit manufacturer’s manual. A standard ELISA kit specific for each of these 6 cytokines to be assayed was purchased from BD PharMingen (San Diego, CA). All of these test procedures were simultaneously carried out by the same technician at the central laboratory of Xiangya Hospital after all serum samples were collected to limit the interassay variability.

Statistics

The data are presented as mean values with their standard deviations (mean +- SD) and analyzed by unpaired t-test. The enumeration data of the patients’ characteristics were analyzed by chi^sup 2^ test. All analyses were performed with SPSS, version 10.0 software (SPSS Inc, Chicago, IL). A statistical value of p < .05 was taken to indicate the statistical significance.

RESULTS

The Preoperative General State of the Subjects’ Health

The subjects’ preoperative state of health is shown in Table I. Before the surgery and LCT treatment, the LCT treatment group and control group of this study were comparable in their age (3.7 +- 1.8 vs 3.3 +- 1.7 years), gender ratio, body weight (14.3 +- 9.0 vs 12.4 +- 8.3 kg), blood albumin (39.0 +- 4.57 vs 37.8 +- 3.98 g/L), liver and renal function, and the surgery types received by the patients. The 2 groups did not differ significantly in terms of each general feature listed above (p > .05, respectively).

The Subjects’ Immune Function Pre- and Postoperation

Neutrophil and PBMC count; lymphocyte percentage and its subsets ratio of CD4/CD8; the serum concentrations of IgA, IgG, IgM, and complement C3 and C4; and cytokines including IL-2, IL-4, IL-10, IL- 12, TNF-alpha, and IFN-gamma, were detected to demonstrate the subjects’ immune function. All these parameters in the LCT group and the control group are summarized in Table II. Before the surgery, the statistics did not show any significant difference between these 2 groups for each of the values listed in Table II; p > .05.

After receiving gastrointestinal operation, each patient’s immune function was determined again at 24 hours and 120 hours postoperatively. An unpaired t-test was used to analyze the difference of each parameter between the LCT treatment group and the control group at the same time point. A small but statistically significant increase in serum IgM was found 24 hours after the operation (p < .05 in the LCT group). There was a significant increase of neutrophil count 24 hours after the surgery in both LCT and control groups compared with that of 24 hours before the operation (p < .01). However, neutrophil count went back to the normal level 120 hours after the operation. There was no significant difference between these 2 groups in any aspect of immune function (Table II; p > .05, respectively).

DISCUSSION

The neutrophil numbers in all patients were found to be significantly increased 24 hours after the operation in this study compared with the preoperative baseline. However, the difference of neutrophil count between the LCT and control groups was not statistically significant at the same time points of 24 hours pre- and postsurgery, respectively. An acute immune reaction after abdominal surgery is supposed to cause a postoperative increase of neutrophil number. The normal neutrophil levels 120 hours postoperative in both LCT and control groups suggest to us that a short-term LCT administration does not affect human neutrophil production. It is documented that lipid emulsion has an impact on mononuclear phagocytic function, particularly phagocytosis.11 LCT infusion was reported to interfere with the production of human PBMC in critically ill children, but this kind of interference was presumed to be related to the infusion dose and speed of LCT.16 We did not find any statistical difference in the postoperative PBMC count at 24 hours and at 120 hours between the LCT group and the control group. We also considered that the lipid tolerance to a short-term LCT administration by our patients may differ from that to a long-term LCT management by critically ill children.

TABLE II

The parameters of the patients’ immune function pre- and postoperation

The proteins of complement C3 and C4 are manufactured in the liver. They circulate in the bloodstream and are activated by the presence of antibodies (thus, they complement their activity). They act to puncture and thus burst, or lyse, foreign cells. Although an in vitro study suggests that LCT emulsions inhibit IL-2-dependent lymphocyte responses in a dose-dependent manner,9 in vivo studies under clinical settings may give us opposite results. In infants, a low-dose intermittent LCT administration at the dose of 1 g/kg/d does not affect their macrophage function, serum levels of C2, C3, and C4, complement components synthesized and secreted exclusively in macrophages.24 In 15 children who received PN for an average of 3 years, these clinically stable children had normal monocyte activation and normal complement C2, C3, and C4 levels.25 The unchanged serum C3 and C4 levels in pediatric patients receiving 5- day LCT treatments found in the present study are consistent with these findings previously described in pediatric patients. Even for patients with acquired immunodeficiency syndrome (AIDS), lacking normal immune function, a prospective, randomized, double-blind, multicenter study shows that LCT at an appropriate dose does not cause any significant abnormalities of lymphocyte subpopulations and function over 6 days.26 The stable lymphocyte populations and its subsets such as CD4, CD8, and CD4:CD8 ratio found in pediatric and adult patients suggest to us that an LCT intervention, which is administered according to the individual body weight at a certain dose and infusion speed, does not significantly influence human cellular immune function.

T cells are thought to play a pivotal part in the initiation of the inflammatory process. Mechanistically, immune responses have been polarized into promoting cell-mediated immunity (Th1) and humoral reaction (Th2) according to their patterns of cytokine production after T-helper (Th) cell activation.27 Th1 responses lead to the secretion of certain proteins called immunoglobulin, as well as IFN-gamma and IL-2.28 The immunoglobulin secreted by special B cells may function by either coating the foreign material so it is recognized by other immune factors that will destroy it or causing destruction of the threat itself. IgA molecules formed 4-6 months after birth generally come in pairs and are found in body secretions, as well as inside the stomach and intestines. IgG secreted 3 months after birth is the main form of immunoglobulin. IgM molecules synthesized in the later stage of the embryo gather in clusters and are involved in killing bacteria. The Th2 phenotype is characterized by secretion of cytokines, such as IL-4 and IL-10.28

To date, there is little information concerning the effects of LCT on human immunoglobulins. A small but statistically significant increase of serum IgA and IgM has been found in 8 normal volunteers receiving a 14-day PN administration.14 But this result must be further confirmed by more cases in substantial clinical conditions. Dahlstrom et al25 pointed out that a 3-year LCT infusion in PN did not alter child subjects’ serum immunoglobulins. Our study demonstrates that a short-term LCT treatment does not significantly change the pediatric patient’s serum levels of IgA and IgG. This result is consistent with Dahlstrom’s findings regarding the effects of a long-term LCT therapy on serum IgA and IgG in pediatric patients. However, a short-term LCT infusion slightly increases the 24-hour postoperative serum IgM level in this study; the etiology and clinical significance of this observation remain unclear. There is evidence that some immunoregulatory cytokines play a pivotal part in inducing the polarization of naive CD4+ T cells after activation into the Th1 or Th2 subsets. In this respect, IL-2 and IFN-gamma are produced mainly by Th1 cells expressing the surface antigen CD4, which could promote T-cell-mediated immune responses. IL-4 and IL- 10 secreted by Th2 cells could inhibit Th1 cytokine release and promote immunoglobulin production.29’30 IL-4 has been shown to be the most potent inducer of Th2-like polarization. It plays an important role in the activation of resting B-cells and the subsequent proliferation and differentiation of B cells. IL-4 is essential for IgE synthesis in vitro. It was also found to inhibit the secretion of IL-1beta, TNF-alpha, and IL-6 of human monocytes, to down-regulate the surface expression of CD5 on B-cells, and to promote the growth of human T-cells.31 IL-10 has been shown to inhibit proinflammatory cytokine production. Neutralization of endogenous IL-4 or IL-10 may initiate or accelerate development of a Thl-associated protective response, whereas IL-12 produced by phagocytic cells and B cells has been identified as the best stimulator of Th1-like differentiation.32 It is reported that LCT emulsions may suppress the lymphocyte response and the cytokine production of TNF-alpha.33 However, there is an opposite opinion that LCT infusion can increase both the Th1 and Th2 lymphocyte levels and TNF-alpha produced by peripheral lymphocytes.34 Although a 30-day LCT treatment is documented to significantly increase the TNF-alpha production by PBMC,35 the data from our study tend to support the finding that LCT exerts no effects on the production of these cytokines.36 Moreover, a clinical trial on postoperative days 1-5 in 21 patients diagnosed with upper digestive tract neoplasm who had undergone radical surgery, and who took the same period of LCT treatment as our pediatric patients, achieved the same endpoint as ours in that LCT administration did not evoke alterations in cytokine production.37 We consider that daily LCT dosage and infusion speed may be the key factor related to the potential influence of LCT on human immune function. Excessive LCT dosage or infusion speed can impose an extra burden on the liver and cause a deposition of LCT in RES and damage phagocytes,38 so as to compromise human immune defense. The child subjects enrolled in this study were administered a certain amount of LCT according to the individual body weight at a low infusion speed; no impaired immune function was observed with respect to IL-2, IL-4, IL-10, IL-12, IFN- gamma, and TNF-alpha.

The differences between the types and numbers of patients studied, and the differences between in vitro and in vivo experiments, may have contributed to the variation in results seen in different studies. However, the results from the current study are shown to be consistent with our recent report obtained from adult patients undergoing gastrointestinal surgery.39 Meanwhile, the daily LCT dosage and infusion speed may be critical to the suspected inhibition influence of LCT on human immune function. Although our findings suggest that a short-term LCT infusion after gastrointestinal surgical procedure at an appropriate dosage and infusion speed has no significant influence on pediatric immune function, we are in favor of the recommendation that enteral nutrition be used in preference to PN.40 We encourage surgical patients to take oral or enteral nutrition as soon as their gastrointestinal conditions permit.

In conclusion, the regimens of LCT administration may have diverse impacts on human immune function in different patient populations. However, LCT emulsions at an appropriate dose and infusion speed do not alter human immune function of pediatric patients following gastrointestinal surgery. The etiology and clinical significance of the slightly increased IgM in child patients 24 hours postoperative remain unclear and must be further investigated.

ACKNOWLEDGMENTS

The study was supported by a grant from the Department of Science and Technology of Hunan Province.

REFERENCES

1. Atkinson M, Worthley LI. Nutrition in the critically ill patient, part II: parenteral nutrition. Crit Care Resusc. 2003;5:121- 136.

2. McCarthy MC, Cottam GL, Turner WW Jr. Essential fatty acid deficiency in critically ill surgical patients. Am J Surg. 1981;142: 747-751.

3. Waitzberg DL, Lotierzo PH, Logullo AF, Torrinhas RS, Pereira CC, Meier R. Parenteral lipid emulsions and phagocytic systems. Br J Nutr. 2002;87(Suppl 1):S49-S57.

4. Kinsella JE. Lipids, membrane receptors, and enzymes: effects of dietary fatty acids. JPEN J Parenter Enteral Nutr. 1990; 14(Suppl 5):S200-S217.

5. Grogos CA, Kalfarentzos FE, Zoumbos NC. Effect of different types of total parenteral nutrition on T-lymphocyte subpopulations and NK cells. Am J Clin Nutr. 1990;51:119-122.

6. Cleary TG, Pickering LK. Mechanisms of Intralipid effect on polymorphonuclear leukocytes. J Clin Lab Immunol. 1983;11: 21-26.

7. Freeman J, Goldmann DA, Smith NE, Sidebottom DG, Epstein MF, Platt R. Association of intravenous lipid emulsion and coagulase- negative staphylococcal bacteremia in neonatal intensive care units. N Engl J Med. 1990;323:301-308.

8. Nordenstrom J, Jarstrand C, Wiernik A. Decreased chemotactic and random migration of leukocytes during Intralipid infusion. Am J Clin Nutr. 1979;32:2416-2422.

9. Sedman PC, Ramsden CW, Brennan TG, Guillou PJ. Pharmacological concentrations of lipid emulsions inhibit interleukin-2-dependent lymphocyte responses in vitro. JPEN J Parenter Enteral Nutr. 1990;14:12-17.

10. Kruimel JW, Naber AH, Curfs JH, Wenker MA, Jansen JB. With medium-chain triglycerides, higher and faster oxygen radical production by stimulated polymorphonuclear leukocytes occurs. JPEN J Parenter Enteral Nutr. 2000;24:107-112.

11. Waitzberg DL, Bellinati-Pires R, Yamaguchi N, et al. Influence of medium-chain triglyceride-based lipid emulsion on rat polymorphonuclear cell functions. Nutrition. 1996;12:93-99.

12. Garnacho-Montero J, Ortiz-Leyba C, Garnacho-Montero MC, et al. Effects of three intravenous lipid emulsions on the survival and mononuclear phagocyte function of septic rats. Nutrition. 2002;18:751-754.

13. Ohta N, Tsujikawa T, Nakamura T, Andoh A, Sasaki M, Bamba T. A comparison of the effects of medium- and long-chain triglycerides on neutrophil stimulation in experimental ileitis. J Gastroenterol. 2003;38:127-133.

14. Buchman AL, Mestecky J, Moukarzel A, Ament ME. Intestinal immune function is unaffected by parenteral nutrition in man. J Am Coll Nutr. 1995;14:656-661.

15. Lenssen P, Bruemmer BA, Bowden RA, Gooley T, Aker SN, Mattson D. Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation. Am J Clin Nutr. 1998;67:927-933.

16. Waitzberg DL, Bellinati-Pires R, Salgado MM, et al. Effect of total parenteral nutrition with different lipid emulsions of human monocyte and neutrophil functions. Nutrition. 1997;13: 128-132.

17. Wiernik A, Jarstrand C, Julander I. The effect of Intralipid on mononuclear and polymorphonuclear phagocytes. Am J Clin Nutr. 1983;37:256-261.

18. Battistella FD, Widergren JT, Anderson JT, Siepler JK, Weber JC, MacColl K. A prospective, randomized trial of intravenous fat emulsion administration in trauma victims requiring total parenteral nutrition. J Trauma. 1997;43:52-60.

19. Cury-Boaventura MF, Gorjao R, de Lima TM, et al. Toxicity of a soybean oil emulsion on human lymphocytes and neutrophils. JPEN J Parenter Enteral Nutr. 2006;30:115-123.

20. Fraser I, Neoptolemos J, Darby H, Bell PR. The effects of Intralipid and heparin on human monocyte and lymphocyte function. JPEN J Parenter Enteral Nutr. 1984;8:381-384.

21. Jensen GL, Mascioli EA, Seidner DL, et al. Parenteral infusion of long- and medium-chain triglycerides and reticuloendothelial system function in man. JPEN J Parenter Enteral Nutr. 1990; 14:467-471.

22. Behrman RE, Kliegman R, Arvin AM, eds. Nelson’s Textbook of Pediatrics. 15th ed. Philadelphia, PA: W.B. Saunders Co; 1996.

23. Reeves GE, Burns C, Hall ST, Gleeson M, Lemmert K, Clancy RL. The measurement of IgA and IgG transglutaminase antibodies in celiac disease: a comparison with current diagnostic methods. Pathology. 2000;32:181-185.

24. Strunk RC, Murrow BW, Thilo E, Kunke KS, Johnson EG. Normal macrophage function in infants receiving Intralipid by low-dose intermittent administration. J Pediatr. 1985;106:640-645.

25. Dahlstrom KA, Goulet OJ, Roberts RL, Ricour C, Ament ME. Lipid tolerance in children receiving long-term parenteral nutrition: a biochemical and immunologic study. J Pediatr. 1988;113: 985-990.

26. Gelas P, Cotte L, Poitevin-Later F, et al. Effect of parenteral medium- and long-chain triglycerides on lymphocytes subpopulations and functions in patients with acquired immunodeficiency syndrome: a prospective study. JPEN J Parenter Enteral Nutr. 1998;22:67-71.

27. Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature. 1996;383:787-793.

28. Salgame P, Abrams JS, Clayberger C, et al. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science. 1991;254:279-282.

29. Lappin MB, Campbell JD. The Th1-Th2 classification of cellular immune responses: concepts, current thinking and applications in haematological malignancy. Blood Rev. 2000;14:228- 239.

30. Kawamura K, Bahar R, Natsume W, Sakiyama S, Tagawa M. Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic antitumor immunity and impairs protective immunity induced against the tumors. Cancer Gene Ther. 2002; 9:109- 115.

31. Maloy KJ, Powrie F. Regulatory T cells in the control of immune pathology. Nat Immunol. 2001;2:816-822.

32. Gattorno M, Picco P, Vignola S, Stalla F, Buoncompagni A, Pistoia V. Serum interleukin 12 concentration in juvenile chronic arthritis. Ann Rheum Dis. 1998;57:425-428. 33. Nordenstrom J, Thorne A, Olivecrona T. Metabolic effects of infusion of a structured- triglyceride emulsion in healthy subjects. Nutrition. 1995;11:269- 274.

34. Monson JR, Ramsden CW, Giles GR, Brennan TG, Guillou PJ. Lymphokine activated killer (LAK) cells in patients with gastrointestinal cancer. Gut. 1987;28:1420-1425.

35. Gogos CA, Zoumbos N, Makri M, Kalfarentzos F. Medium- and long-chain triglycerides have different effects on the synthesis of tumor necrosis factor by human mononuclear cells in patients under total parenteral nutrition. J Am Coll Nutr. 1994;13:40-44.

36. Wanten GJ, Netea MG, Naber TH, et al. Parenteral administration of medium- but not long-chain lipid emulsions may increase the risk for infections by Candida albicans. Infect Immun. 2002; 70:6471-6474.

37. Arias-Diaz J, Rodriguez JM, Vara E, et al. NO2/NO3 and cytokine plasma profiles under different postoperative parenteral nutrition regimens. Nutrition. 1996;12:89-92.

38. Kuse ER, Kotzerke J, Muller S, Nashan B, Luck R, Jaeger K. Hepatic reticuloendothelial function during parenteral nutrition including an MCT/LCT or LCT emulsion after liver transplantation: a double-blind study. Transplant Int. 2002;15:272-277.

39. Li X, Ying J, Zeng S, Shen L, Wan X, Li X, et al. A short- term long-chain triglycerides infusion has no influence on immune function of adult patients undergoing gastrointestinal surgery. JPEN J Parenter Enteral Nutr. 2007;31:167-172.

40. Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003;27:355-373.

Xiaogang Li, MD*; Jiaoqian Ying, MD*; Shan Zeng, MD[dagger]; Yixiong Li, MD[double dagger]; Huixiang Yang, MD[double dagger]; Liangfang Shen, MD[dagger]; Jie Han, MD*; Jia Chen, MD[dagger]; and Hong Shen, MD[section]

From the * Department of Surgery, [dagger] Department of Oncology, [double dagger] Department of Gastroenterology, and [section] Medical Research Center, Xiangya Hospital,

Central South University, Changsha, Hunan, China

Received for publication May 14, 2007.

Accepted for publication June 18, 2007.

Correspondence: Hong Shen, Yixiong Li, or Huixiang Yang, Xiangya Hospital, Central South University, Changsha, Hunan, China 410008. Electronic mail may be sent to hongshen2000@yahoo.com, liyixiong6@hotmail.com, or yang_hx430@163.com.

Copyright American Society for Parenteral and Enteral Nutrition Jan/ Feb 2008

(c) 2008 JPEN, Journal of Parenteral and Enteral Nutrition. Provided by ProQuest Information and Learning. All rights Reserved.