|
Sign In to gain access to subscriptions and/or personal tools.
|
Influence of Adding Fish Oil to Parenteral Nutrition on Gut-Associated Lymphoid Tissue
Yoshinori Maeshima, MD*,
Kazuhiko Fukatsu, MD, PhD ,
Tomoyuki Moriya, MD ,
Fumie Ikezawa, MD,
Chikara Ueno, MD*,
Daizoh Saitoh, MD, PhD and
Hidetaka Mochizuki, MD, PhD*
From the * Department of Surgery, National Defense
Medical College, Saitama, Japan; Division of
Basic Traumatology, National Defense Medical College Research Institute,
Saitama, Japan; and the Department of Surgery,
Chiba University, Chiba, Japan
Correspondence: Kazuhiko Fukatsu, MD, PhD, Division of Basic Traumatology,
National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa,
Saitama, Japan 359-8513. Electronic mail may be sent to
fukatsu{at}ndmc.ac.jp.
Background: Lack of enteral nutrition reduces gut-associated
lymphoid tissue (GALT) mass and function, a mechanism underlying the increased
morbidity of infectious complications in severely injured or critically ill
patients. Strategies to restore parenteral nutrition (PN)–induced
changes of GALT mass and function have been pursued. However, the influences
of adding fish oil to PN on gut immunity remain to be clarified.
Methods: Male Institute of Cancer Research (ICR) mice (n = 50) were
randomized to 4 groups: ad libitum chow (chow), fat free PN (fat
(–)-PN), PN + fish oil (FO-PN), and PN + safflower oil (SO-PN). The PN
groups were given isocaloric and isonitrogenous PN solutions. The FO- and
SO-PN groups received 20% of total calories from fat emulsions. After 5 days
of feeding, lymphocytes from Peyer's patches (PPs), the intraepithelial space
(IE), and the lamina propria (LP) of the entire small intestine were isolated.
GALT lymphocyte numbers and phenotypes (CD4+, CD8+,  βTCR+,
  TCR+, B220+ cells) were determined. Immunoglobulin A (IgA)
levels of small intestinal washings were also measured by enzyme-linked
immunosorbent assay. Another set of mice (n = 24) was used to determine plasma
fatty acid compositions after feeding. Results: Lymphocyte numbers
from PPs and the LP and intestinal IgA levels were significantly lower in the
PN groups than in the chow group, with no significant differences between any
2 PN groups. The FO- and SO-PN groups showed moderate recovery of IE cell
numbers compared with the fat (–)-PN group.  -3 and  -6
fatty acid levels were increased with fish and safflower oil additions,
respectively, compared with the fat (–)-PN group. Conclusions:
Adding fish oil to PN does not exacerbate PN-induced GALT changes but rather
partially reverses these changes, with increased plasma -3 fatty acid
levels.
Recent advancements in immunology have led to a better understanding of the
role of nutrition in host responses to various surgical insults. Nutrition is
now recognized to modulate and improve immune responses, as well as to provide
energy and
nitrogen.1 Modern
nutrition therapy includes early enteral nutrition and immune-enhancing diets.
Clinical benefits of these nutrition interventions have been demonstrated in
randomized controlled
studies.2–4
-3 polyunsaturated fatty acids (PUFAs) are important constituents of
many immune-enhancing diets available for clinical
use.5 While
-6 PUFAs have been demonstrated to enhance the inflammatory response
and suppress host immunity through production of potent inflammatory mediators
such as prostaglandin (PG)-2 and leukotriene (LT)-4 series eicosanoids,
dietary supplementation of -3 PUFAs reportedly alters the cell membrane
composition, with decreased production of these eicosanoids but increased
production of the less inflammatory and more immunocompetent PG-3 and LT-5
series.6,7
Thus, unlike other immunonutrients, such as arginine, glutamine, and
nucleotides, -3 PUFAs do not stimulate the immune system. Instead,
-3 PUFAs aid the immune system by competing with arachidonic acid for
cyclo-oxygenase metabolism at the cell
membrane.6,7
Though enteral formulas containing immunonutrients are considered to have
strong effects on host immunity, some patients do not benefit from enteral
nutrition due to bowel obstruction, splanchnic hypoperfusion, or
gastrointestinal (GI) tract bleeding. To provide immunonutrients to these
critically ill and severely injured patients, parenteral immunonutrition
formulas have been developed. New parenteral formulas, such as
alanyl-glutamine dipeptide solution and -3 PUFA emulsions, are still
not clinically available in Japan or the United States. However, clinical data
from the use of these formulas (ie, effects on host response) have already
been demonstrated in some European and other
countries.8–11
To date, no marked disadvantages of -3 PUFA-rich parenteral
nutrition (PN) have been reported in terms of gut immunity. To the contrary,
enteral administration of -3 PUFAs with glutamine and fructose
diphosphate was shown to increase the mucosal cell proliferative index and to
decrease the apoptotic index in a small bowel graft
model.12 However,
it is possible that -3 PUFA-supplemented parenteral solutions
exacerbate PN-induced gut-associated lymphoid tissue (GALT) atrophy and
dysfunction, in the absence of other nutrients with trophic effects on the
mucosa and lymphoid tissue. -3 PUFAs are by themselves known to induce
marked apoptosis and to reduce proliferation of immune cells and gut mucosal
cells.13–16
Dietary -3 PUFAs induced higher apoptosis of splenocytes by increasing
the generation of lipid peroxides and elevating Fas-L expression along with
decreasing Bcl-2 expression when these cells were stimulated with anti-CD3 and
anti-Fas
antibody.13 When
human blood lymphocytes were stimulated in vitro with polyclonal
antigens, addition of -3 fatty acids (eicosapentaenoic acid,
docosahexaenoic acid) to the medium inhibited their
proliferation.14
Phytohemagglutinin-induced proliferation of mononuclear cells was suppressed
by 70% after -3 fatty acid supplementation of a normal
diet.15 Moreover,
incorporation of eicosapentaenoic acid into colonic epithelial cell lipids was
reported to increase
apoptosis.16
Therefore, we designed this study to examine the influences of adding
-3 and -6 PUFAs to PN on GALT mass and function in a murine
model. We used fish oil and safflower oil emulsions as significant sources of
-3 fatty and -6 fatty acids, respectively. We randomized mice to
fat-free PN, PN + safflower oil, PN + fish oil, and chow groups. The ad
libitum chow group served as well-nourished controls receiving a normal
diet and underwent the same surgical procedure as did the PN groups.
 |
MATERIALS AND METHODS
|
|---|
Animals
Specific, pathogen-free, 6- to 7-week-old, male Institute of Cancer
Research (ICR; Nippon SLC, Hamamatsu, Japan) mice were housed under controlled
temperature (24°C) and humidity (60%) conditions with a 12-hour:12-hour
light:dark cycle. Mice were fed standard chow (CE7; Clea Japan, Tokyo, Japan)
containing protein, fat, carbohydrate, cellulose, minerals, and a vitamin mix
with water ad libitum for 1 week before protocol entry. All studies
were approved by the Animal Experiment Committee of the National Defense
Medical College.
Surgical Procedure
Seventy-four mice were given general anesthesia (ketamine hydrochloride 100
mg/kg and xylazine 10 mg/kg mixture) and randomized into 4 groups: ad
libitum chow (chow: n = 18), fat-free PN (fat (–)-PN: n = 15), PN +
fish oil (FO-PN: n = 20), or PN + safflower oil (SO-PN: n = 21). All mice
underwent implantation of silicon rubber catheters (Imamura Co, Tokyo, Japan;
0.014-inch inner diameter/0.026-inch outer diameter) into the right jugular
vein. A silicon rubber catheter was inserted into the vena cava via
the right internal jugular. The proximal end of the catheter was tunneled
subcutaneously over the spine and exited the tail at its midpoint. The mice
were placed in metal metabolism cages and partially immobilized by tail
restraint to protect the catheter during infusion. This technique is an
acceptable method of nutrition support that does not induce physical or
biochemical
stress.17
Catheterized mice were immediately connected to an infusion pump (TE-331;
Terumo, Tokyo, Japan).
Experimental Design and Nutrition Support
Catheterized mice were given a 0.9% NaCl solution, 4.8 mL/d, and allowed
ad libitum access to chow (CE-7) and water for 48 hours to promote
recovery from surgical stress (Figure
1). The chow control group received chow ad libitum and
water, with continuous infusion of 0.9% NaCl saline, 4.8 mL/d, via a
jugular vein catheter. The PN groups were given isocaloric and isonitrogenous
standard PN solutions with or without fat emulsion. These PN solutions
provided 1230 kcal/L, with a nonprotein calorie/nitrogen ratio of 208:1 kcal/g
nitrogen (Table I). The PN
solutions were supplemented with micronutrients (Elemenmic; Ajinomoto, Tokyo,
Japan) and multivitamins (M.V.I-SS, SS-seiyaku Co, Tokyo, Japan). The SO- and
FO-PN groups received 20% of total calories from fat emulsions. Part of the
carbohydrate in the fat (–)-PN solution was replaced by safflower oil or
fish oil, without changing the amino acid composition. The fish oil emulsion
(Omegaven; Fresenius-Kabi, Bad Homberg, Germany) contained 10% fish oil
(eicosapentaenoic acid 12.5–28.2, docosahexaenoic acid 14.4–30.9
g/L of fat emulsion). The safflower oil emulsion contained 10% safflower oil
(linoleic acid 73.5 g/L of fat emulsion). The PN groups were advanced from 9.6
mL/d of PN solution to a target rate of 16.8 mL/d (20.7 kcal/d) by the third
day of feeding (day 1, 0.4 mL/h; day 2, 0.5 mL/h; days 3–5, 0.7 mL/h)
because a graded infusion period was demonstrated to be necessary to allow the
mice to adapt to the glucose and fluid
load.18 The target
rate for the PN solution was determined according to our previous data from
ad libitum chow–fed mice. The chow mice consumed approximately
6–6.5 g of chow (20.4–22.1 kcal) per day in this setting.
View larger version (9K):
[in this window]
[in a new window]
|
FIGURE 1. Feeding protocol. Daily food intakes for days 1–7 (chow, n = 12; fat
(–)-PN, n = 9; FO-PN, n = 14; SO-PN, n = 15) are shown. The chow group
received a saline infusion with free access to chow and water throughout the
feeding period. After day 2, the parenteral (fat (–)-PN, FO-PN, and
SO-PN) groups were advanced from 9.6 mL/d PN solution to a target rate of 16.8
mL/d (20.7 kcal/d) by the third day of feeding (day 3, 0.4 mL/h; day 4, 0.5
mL/h; days 5–7, 0.7 mL/h). FO, fish oil emulsion; GALT, gut-associated
lymphoid tissue; PN, parenteral nutrition; SO, safflower oil emulsion.
|
|
Experiment 1: GALT Mass and Function
Fifty mice (chow: n = 12; fat (–)-PN: n = 9; FO-PN: n = 14; SO-PN: n
= 15) were used for GALT lymphocyte isolation and measurement of small
intestinal immunoglobulin A (IgA) levels.
GALT isolation. Lymphocytes were isolated from GALT using a
modification of the method described by Li et
al.19 Peyer's
patches (PPs) were examined as an inductive tissue for mucosal immunity.
Lymphocytes of the intraepithelial (IE) space and lamina propria (LP) were
chosen as gut mucosal immunity effector sites.
PPs. PPs were excised from the serosal side of the intestine and
then teased apart. The fragments were treated with collagenase (Sigma, St.
Louis, MO; 40 U/mL) in RPMI1640 for 60 minutes at 37°C, with constant
shaking. After collagenase digestion, the cell suspensions were passed through
nylon filters.
IE and LP cells. After PP excision, the intestine was turned
inside out and cut into 4 segments. The segments were incubated with RPMI1640
containing 5% fetal bovine serum (FBS), 1% glutamine, and a 1% antibiotic
mixture (penicillin and streptomycin; GIBCO, Auckland, New Zealand), for 45
minutes at 37°C in a water shaker (150 rpm). Supernatants containing
released sloughed epithelial cells and IE lymphocytes were stored on ice. The
remaining tissue pieces were incubated 3 times, 45 minutes each time, with
RPMI1640 containing collagenase (Sigma; 40 U/mL), 5% FBS, glutamine, and an
antibiotic mixture at 37°C at 150 rpm in a water shaker. Supernatants
containing LP cells from each incubation were pooled on ice. Supernatants were
filtered through a glass wool column. Suspensions were centrifuged, the
pellets were resuspended in 40% Percoll (Pharmacia, Piscataway, NJ), and the
cell suspensions were overlaid on 75% Percoll. After centrifugation for 20
minutes at 600 g at 25°C, viable lymphocytes were recovered and
washed in RPMI1640. The lymphocytes were resuspended in RPMI1640 with 5% FBS,
1% glutamine, and the 1% antibiotic mixture and then counted. This procedure
yields a cell population that is 95%–100% viable by trypan blue
exclusion.
Flow cytometry. Lymphocytes (1 x 105) isolated
from PPs, the IE space, and the LP were suspended in 50 µL HBSS containing
fluorescein isothiocyanate (FITC) antimouse TCR (clone GL3;
Caltag, Burlingame, CA) and phycoerythrin (PE) conjugated antimouse βTCR
(clone H57–597; Pharmingen, San Diego, CA) to identify
TCR+ T cells and βTCR+ T cells, respectively, or
PE-anti-CD4 (clone CT-CD4; Caltag) and FITC-anti-CD8 (clone CT-CD8a;
Caltag) to identify the 2 T-cell subsets or FITC-anti-CD45R (B220; clone
RA3–6B2; Caltag) to identify B cells. All antibodies were diluted to 1
µg/mL in HBSS containing 1% FBS. Incubations were carried out for 30
minutes on ice. After staining, the cells were washed twice in HBSS/1% FBS and
then fixed in 1% paraformaldehyde. Flow cytometric analyses were performed on
an Epics XL (Coulter, Hileah, IL).
IgA quantification. Immunoglobulin A was measured in intestinal
washings in a sandwich enzyme-linked immunosorbent assay using a polyclonal
goat anti-mouse IgA (Sigma) to coat the plate, a purified mouse IgA (Zymed
Laboratories, San Francisco, CA) as the standard, and a horseradish
peroxidase– conjugated goat-antimouse IgA (Sigma).
Experiment 2: Plasma Fatty Acid Composition
Twenty-four mice (n = 6 in each group) were used for plasma fatty acid
composition measurement. After 5 days of feeding, blood was obtained by
cardiac puncture under anesthesia. Total lipids from 0.1 mL of plasma were
extracted with chloroform:methanol (2:1, vol/vol) containing 50 mg/L
2,6-di-t-butyl-4-methylphenol.20
The chloroform extract was concentrated by evaporation under nitrogen. For
esterification, the lipids were boiled under reflux conditions for 7 minutes
with 0.46 mL of 0.5 M methanolic sodium hydroxide solution, 0.6 mL of 14%
methanolic boron trifluoride was added, and the mixture was boiled under
reflux conditions for another 30 minutes. The reaction mixture was extracted
with 0.35 mL of isooctane and 2 mL of saturated sodium chloride solution. The
fatty acid composition of the upper isooctane layer was analyzed by gas
chromatography.21,22
Statistical analysis. Results are presented as mean ± SE.
Statistical significance was determined using a 1-way ANOVA, followed by a
post hoc Fisher's protected least significant difference test. A
value of p < .05 was considered to represent a statistically
significant difference.
View larger version (11K):
[in this window]
[in a new window]
|
FIGURE 2. Numbers of GALT lymphocytes. Values are mean ± SE. *p < .05 vs
chow. FO, fish oil emulsion; PN, parenteral nutrition; SO, safflower oil
emulsion.
|
|
|
RESULTS
|
|---|
Experiment 1
Body weight change. At the beginning of the experiment, there were
no significant differences in body weight among the groups
(Table II). After feeding, the
fat (–)-PN group gained significantly less weight than the other 3
groups. There were no significant differences in weight gain among the chow,
FO-, and SO-PN groups.
Total cell yields from GALT. PP lymphocyte numbers were
significantly lower in the fat (–)-, FO-, and SO-PN groups than in the
chow group (Figure 2). The FO-
and SO-PN groups did not show marked changes compared with the fat
(–)-PN group.
The IE lymphocyte numbers were significantly lower in the fat (–)-PN
than in the chow group. Those of the FO- and SO-PN groups were midway between
those of the chow and fat (–)-PN groups.
With regard to the LP, lymphocyte numbers were significantly lower in the
fat (–)-, FO-, and SO-PN groups than in the chow group. LP lymphocyte
numbers were similar in the fat (–)-, FO-, and SO-PN groups, with no
significant differences among the 3 PN groups.
Absolute numbers of βTCR+,
TCR+, CD4+, CD8+, and B220+
cells in GALT. Absolute numbers of βTCR+, CD4+, and B220+
cells in PPs, βTCR+, TCR+, CD4+, and CD8+ cells in
IE spaces and TCR+ cells in the LP were significantly lower in
the fat (–)-, 3-, and 6-PN groups than in the chow group,
without significant differences among the fat (–)-, FO-, and SO-PN
groups (Table III).
The fat (–)- and FO-PN groups showed significantly lower PP
TCR+ and IE B220+, as well as LP βTCR+ and CD8+,
cell numbers than the chow group.
The PP CD8+ cell numbers were significantly lower in the fat (–)-PN
than in the chow group, whereas the FO- and SO-PN groups did not show
significant reductions compared with the chow group.
Intestinal IgA levels. Intestinal IgA levels in the chow group
were significantly higher than those in the fat (–)-, FO-, and SO-PN
groups, whereas there were no significant differences among the 3 PN groups
(Figure 3).
View larger version (15K):
[in this window]
[in a new window]
|
FIGURE 3. Intestinal IgA levels. Values are mean ± SE. *p < .05 vs chow.
FO, fish oil emulsion; PN, parenteral nutrition; SO, safflower oil
emulsion.
|
|
Experiment 2
Plasma -3 fatty acid levels were significantly higher in the FO-PN
than in the other groups. The fat (–)- and SO-PN groups had
significantly lower -3 fatty acid levels than the chow group
(Figure 4A). The chow and SO-PN
groups both had significantly higher -6 fatty acid levels than the fat
(–)- and FO-PN groups (Figure
4B).
|
DISCUSSION
|
|---|
In the present study, the fat-free PN group had significantly lower PP, IE,
and LP lymphocyte numbers and intestinal IgA levels than the chow group, which
is consistent with previous reports by the Kudsk
group.23,24
Addition of fish or safflower oil had minimal effects on GALT cell numbers,
producing partial recovery of IE lymphocyte numbers. Fish oil supplementation
had no detrimental effects on gut immunity, in comparison to the fat-free PN
group.
Naïve lymphocytes migrate from the bloodstream across PP high
endothelial venules and are sensitized to antigens. Sensitized lymphocytes
move to mesenteric lymph nodes, travel via the thoracic duct and home
to intestinal (IE space and LP) or extraintestinal mucosal
sites.25,26
GALT is thus considered to be a center of systemic mucosal immunity.
Experimental and clinical research has linked GALT mass atrophy and
dysfunction during PN to increased susceptibility to infectious
complications.19,23,26–30
In these studies, animals were fed fat-free or -6 PUFA-supplemented PN
solutions.23,26–29
Because fat amounts and compositions of fat may affect the host inflammatory
response, with the possible influence of nutrition route on host immunity
being unclear, fat-free PN solutions have frequently been administered in
animal studies. Because the main component of fat emulsions used in clinical
settings has been -6 PUFA, PN with -6 PUFAs was the most widely
studied composition in animal models. To our knowledge, effects of parenteral
-3 PUFAs on GALT have not previously been examined. Because -3
PUFA parenteral solutions may be given to patients with the expectation of
normalizing host immunity, we considered it to be important to determine
whether these solutions have any beneficial or detrimental effects on GALT. In
the present study, we used fish and safflower oil as significant sources of
3- and 6-fatty acids, respectively.
According to our findings, adding fish oil to PN does not accelerate
PN-induced GALT changes, nor does it change the phenotypic pattern of GALT
lymphocytes. On the contrary, both fish and safflower oil appeared to
partially reverse PN-induced IE cell loss. The precise mechanisms underlying
these phenomena are not clear from the present results, because we did not
examine either apoptosis or proliferation of GALT lymphocytes. Moreover,
whether adding fat changed prostanoid production in GALT in the present
setting was not evaluated. However, plasma fatty acid compositions changed
markedly with fish oil addition in experiment 2, suggesting the PUFA dose
given to mice in the present study are apparently sufficient to produce
immunomodulatory effects in vivo.
Fat-free PN has been demonstrated to decrease gut IgA-stimulating cytokine
levels while not changing gut IgA-inhibiting cytokine levels, which is
presumably an important mechanism underlying the low secretory IgA levels
observed in the absence of enteral
nutrition.26,31
Dietary -3 PUFAs reportedly increase breast milk IgA levels in
association with enhanced levels of IgA-stimulating cytokines (IL-10 and
IL-6).32 A
synthetic -3 PUFA was demonstrated to inhibit T lymphocyte production
of the IgA-inhibiting cytokines TNFβ and
IFN.33 Thus,
in terms of the maintenance of secretory IgA levels, one might have expected
the PN + fish oil group to have shown beneficial effects, compared with the PN
+ safflower oil and fat-free PN groups. However, there were no significant
differences in small intestinal IgA levels between any 2 of the PN-fed groups
in the current study. It is possible that adding fat does not exert direct
effects on the gut cytokine milieu in this setting.
Various mechanisms associated with PN can impair gut immunity. Lack of a
direct nutrition supply from the gut lumen to the mucosa and absence of
glutamine, an important energy substrate for both immune and gut epithelial
cells, in PN solution, decreased neuropeptide release and increased apoptosis
of GALT lymphocytes. These changes, together with alterations in the
lymphocyte homing system and gut cytokine milieu, may all contribute to
impaired gut immunity during
PN.24,34
The present study suggests that fat administration does not have strong
effects on GALT mass or function in uninjured patients during the short period
of PN. Nevertheless, we need to determine whether -3 and -6 PUFA
addition to PN affects GALT in the settings of various insults. Of course,
long-term administration of fat-free PN may have deleterious effects on GALT
even in uninjured states because fat is an essential cell membrane component
and a precursor of several important mediators.
In the present study, we did not include animals receiving both fish and
safflower oil. Healthy subjects generally ingest various types of fat, at
various ratios of -3 and -6 PUFAs, from foods. There might be an
optimal -3/-6 PUFA rate for preservation of GALT. In a future
study, we plan to assess this possibility. We should also keep in mind that
fish oil includes other components that might have affected the results and
that the profile of fish oil differs significantly from that of flax seed oil,
another significant source of -3 fatty acids. Therefore, we cannot
conclude that all -3 fatty acids have the same effects on GALT as those
demonstrated in the present study.
|
SUMMARY
|
|---|
Although dietary -3 PUFAs have been demonstrated to increase
apoptosis and decrease proliferation of immune cells and gut mucosal cells, we
confirmed that adding fish oil to PN at 20% of total calories does not further
exacerbate PN-induced GALT atrophy or dysfunction. Clinicians may be able to
prescribe PN solutions with fish oil without concern as to possible
detrimental effects on GALT. However, unlike glutamine, infusion of a fish oil
emulsion has no marked beneficial impact on GALT maintenance during PN. The
most appropriate immunonutrients for PN should be tailored to the conditions
of individual patients.
We thank A. Hagi (Otsuka Pharmaceutical Factory, Inc) for his important
contributions to the experiments.
Received for publication April 25, 2006.
Accepted for publication March 30, 2007.
- Moore FA. Effects of immune-enhancing diets on infectious morbidity
and multiple organ failure. JPEN J Parenter Enteral Nutr.2001; 25(2 suppl):S36
–S42.[Free Full Text]
- Senkal M, Haaker R, Linseisen J, Wolfram G, Homann HH, Stehle P.
Preoperative oral supplementation with long-chain omega-3 fatty acids
beneficially alters phospholipid fatty acid patterns in liver, gut mucosa, and
tumor tissue. JPEN J Parenter Enteral Nutr.2005; 29:236
–240.[Abstract/Free Full Text]
- Bastian L, Weimann A. Immunonutrition in patients after multiple
trauma. Br J Nutr.2002; 87(suppl 1):S133
–S134.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should
immunonutrition become routine in critically ill patients? A systematic review
of the evidence. JAMA.2001; 286:944
–953.[Abstract/Free Full Text]
- Consensus recommendations from the US Summit on Immune-Enhancing
Enteral Therapy. JPEN J Parenter Enteral Nutr.2001; 25(2 suppl):S61
–S63.[Free Full Text]
- Furst P, Kuhn KS. Fish oil emulsions: what benefits can they bring?Clin Nutr.
2000;19:7
–14.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty
acids and inflammatory mediator production. Am J Clin Nutr.2000; 71(1 suppl):343S
–348S.[Abstract/Free Full Text]
- Heller AR, Rossler S, Litz RJ, et al. Omega-3 fatty acids improve
the diagnosis-related clinical outcome. Crit Care Med.2006; 34:972
–979.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Roulet M, Frascarolo P, Pilet M, Chapuis G. Effects of
intravenously infused fish oil on platelet fatty acid phospholipid composition
and on platelet function in postoperative trauma. JPEN J Parenter
Enteral Nutr. 1997;21:296
–301.[Abstract/Free Full Text]
- Yao GX, Xue XB, Jiang ZM, Yang NF, Wilmore DW. Effects of
perioperative parenteral glutamine-dipeptide supplementation on plasma
endotoxin level, plasma endotoxin inactivation capacity and clinical outcome.Clin Nutr.
2005;24:510
–515.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Hulsewe KW, van Acker BA, Hameeteman W, et al. Does
glutamine-enriched parenteral nutrition really affect intestinal morphology
and gut permeability? Clin Nutr.2004; 23:1217
–1225.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Wu XT, Li JS, Zhao XF, et al. Effects of n-3 fatty acid,
fructose-1,6-diphosphate and glutamine on mucosal cell proliferation and
apoptosis of small bowel graft after transplantation in rats. World J
Gastroenterol. 2003;9:1323
–1326.[Web of Science][Medline]
[Order article via Infotrieve]
- Avula CP, Zaman AK, Lawrence R, Fernandes G. Induction of apoptosis
and apoptotic mediators in Balb/C splenic lymphocytes by dietary n-3 and n-6
fatty acids. Lipids.1999; 34:921
–927.[Web of Science][Medline]
[Order article via Infotrieve]
- Purasiri P, McKechnie A, Heys SD, Eremin O. Modulation in
vitro of human natural cytotoxicity, lymphocyte proliferative response to
mitogens and cytokine production by essential fatty acids.Immunology.
1997;92:166
–172.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Endres S, Meydani SN, Ghorbani R, Schindler R, Dinarello CA.
Dietary supplementation with n-3 fatty acids suppresses interleukin-2
production and mononuclear cell proliferation. J Leukoc Biol.1993; 54:599
–603.[Abstract]
- Latham P, Lund EK, Brown JC, Johnson IT. Effects of cellular redox
balance on induction of apoptosis by eicosapentaenoic acid in HT29 colorectal
adenocarcinoma cells and rat colon in vivo. Gut.2001; 49:97
–105.[Abstract/Free Full Text]
- Sitren HS, Heller PA, Bailey LB, Cerda JJ. Total parenteral
nutrition in the mouse: development of a technique. JPEN J Parenter
Enteral Nutr. 1983;7:582
–586.[Abstract/Free Full Text]
- Mahaffey SM, Copeland EM III, Talbert JL, Baumgartner TG, Sitren
HS. Further studies of a technique for total parenteral nutrition in the
mouse. Nutr Res. 1985;5:1121
–1130.[CrossRef][Web of Science]
- Li J, Kudsk KA, Gocinski B, Dent D, Glezer J, Langkamp-Henken B.
Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue.J Trauma.
1995;39:44
–51; discussion 51–52.[Web of Science][Medline]
[Order article via Infotrieve]
- Folch J, Lees M, Sloane Stanley GH. A simple method for the
isolation and purification of total lipids from animal tissues. J Biol
Chem. 1957;226:497
–509.[Free Full Text]
- Metcalfe LD, Schmitz AA, Pelka JR. Rapid preparation of fatty acid
esters from lipids for gas chromatographic analysis. Anal Chem.1966; 38:514
–515.
- Bannon CD, Craske JD, Hai NT, Harper NL, O'Rourke KL. Analysis of
fatty acid methyl esters with high accuracy and reliability, II: methylation
of fats and oils with boron trifluoride-methanol. J Chromatogr
A. 1982;247:63
–69.[CrossRef]
- Kudsk KA, Li J, Renegar KB. Loss of upper respiratory tract
immunity with parenteral feeding. Ann Surg.1996; 223:629
–635.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Johnson CD, Kudsk KA. Nutrition and intestinal mucosal immunity.Clin Nutr.
1999;18:337
–344.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Salmi M, Jalkanen S. Lymphocyte homing to the gut: attraction,
adhesion, and commitment. Immunol Rev.2005; 206:100
–113.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- King BK, Kudsk KA, Li J, Wu Y, Renegar KB. Route and type of
nutrition influence mucosal immunity to bacterial pneumonia. Ann
Surg. 1999;229:272
–278.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Johnson CD, Kudsk KA, Fukatsu K, Renegar KB, Zarzaur BL. Route of
nutrition influences generation of antibody-forming cells and initial defense
to an active viral infection in the upper respiratory tract. Ann
Surg. 2003;237:565
–573.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Alverdy JA, Aoys E, Weiss-Carrington P, Burke DA. The effect of
glutamine-enriched TPN on gut immune cellularity. J Surg Res.1992; 52:34
–38.[Web of Science][Medline]
[Order article via Infotrieve]
- Wildhaber BE, Yang H, Teitelbaum DH. Total parenteral
nutrition-induced apoptosis in mouse intestinal epithelium: modulation by
keratinocyte growth factor. J Surg Res.2003; 112:144
–151.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Okamoto K, Fukatsu K, Ueno C, et al. T lymphocyte numbers in human
gut associated lymphoid tissue are reduced without enteral nutrition.JPEN J Parenter Enteral Nutr.2005; 29:56
–58.[Abstract/Free Full Text]
- Wu Y, Kudsk KA, DeWitt RC, Tolley EA, Li J. Route and type of
nutrition influence IgA-mediating intestinal cytokines. Ann
Surg. 1999;229:662
–667.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Dunstan JA, Roper J, Mitoulas L, Hartmann PE, Simmer K, Prescott
SL. The effect of supplementation with fish oil during pregnancy on breast
milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid
composition. Clin Exp Allergy.2004; 34:1237
–1242.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Costabile M, Hii CS, Robinson BS, et al. A novel long chain
polyunsaturated fatty acid, beta-Oxa 21:3n-3, inhibits T lymphocyte
proliferation, cytokine production, delayed-type hypersensitivity, and
carrageenan-induced paw reaction and selectively targets intracellular
signals. J Immunol.2001; 167:3980
–3987.[Abstract/Free Full Text]
- Kudsk KA. Current aspects of mucosal immunology and its influence
by nutrition. Am J Surg.2002; 183:390
–398.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
Journal of Parenteral and Enteral Nutrition, Vol. 31, No. 5,
416-422 (2007)
DOI: 10.1177/0148607107031005416
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
|
|
Top
MATERIALS AND METHODS
RESULTS