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K A Kudsk

Publications and source records attributed to K A Kudsk.

At least 19 recordsLinked to original sources
PubMed2001

Lack of enteral feeding increases expression of E-selectin after LPS challenge.

BACKGROUND: Total parenteral nutrition (IV-TPN) increases neutrophil accumulation in the small intestine, expression of intestinal ICAM-1 and P-selectin, and upregulates E-selectin expression in the lung. Endothelial activation induced by lack of enteral nutrition may change the response to injury or infection. This study investigated whether nutrition influenced the expression of the adhesion molecule, E-selectin and ICAM-1, following endotoxin challenge. MATERIALS AND METHODS: Forty-three mice were injected with saline, 2, 20, 200, 2000, or 10000 microg/kg lipopolysaccharide (LPS) intraperitoneally. E-selectin expression in the lung, small intestine, and heart was quantified at 3 h after challenge, while ICAM-1 was measured at 5 h, using the dual-radiolabeled monoclonal antibody technique. Next, 80 mice were fed chow, intragastric (IG)-TPN, or IV-TPN for 5 days, and then received intraperitoneal 2 or 200 microg/kg LPS. E-selectin and ICAM-1 expression in organs was measured at 3 and 5 h after endotoxin, respectively. RESULTS: E-selectin expression in organs increased LPS dose dependently. ICAM-1 levels reached early peaks in the lung and in the intestine. Also, IV-TPN significantly increased E-selectin expression in the small intestine and tended to increase pulmonary E-selectin, when compared to chow or IG-TPN animals. There were no significant differences in E-selectin expression among three diet groups after 200 microg/kg LPS challenge. No differences in ICAM-1 expression were observed in any organ among the three groups after 2 or 200 microg/kg LPS injection. CONCLUSIONS: E-selectin rather than ICAM-1, because of the expression pattern after various dosages of LPS challenge, may be a determining factor for the degree of LPS-induced inflammation at the early phase. Lack of enteral nutrition may increase inflammatory response through enhanced gut E-selectin levels after a small dose of LPS.

Animals↗
PubMed2001

Impairment of mucosal immunity by total parenteral nutrition: requirement for IgA in murine nasotracheal anti-influenza immunity.

Secretory IgA (SIgA) is the primary mucosal Ig and has been shown to mediate nasotracheal (NT) mucosal immunity in normal immune BALB/c mice. This finding has been challenged by a report of NT immunity without IgA in knockout mice, suggesting that IgA may not be necessary for the protection of mucosal surfaces. Although other protective mechanisms may become active in the congenital absence of SIgA, these mechanisms are not the primary means of protection in normal mice. In this paper we show that feeding chemically defined total parenteral nutrition (TPN) to genetically normal, immune ICR mice by the i.v. route results in loss of nasal anti-influenza immunity and a significant drop in influenza-specific SIgA in the upper respiratory tract compared with chow-fed mice (p < 0.005), while the serum influenza-specific IgG titer is unaffected. Loss of upper respiratory tract mucosal immunity is not related to serum Ab, because 10 of 13 TPN-fed mice shed virus into their nasal secretions despite adequate serum anti-influenza IgG titers. The number of IgG Ab-secreting cells in the nasal passages and spleens of TPN-fed mice was unaffected, while both the number and the percentage of splenic IgA-secreting cells were decreased relative to those in chow-fed animals. The loss of immunity is due to the route of nutrition, not the composition of the diet, because TPN solution fed orally via gastrostomy instead of i.v. maintains NT anti-influenza mucosal immunity. We hypothesize that delivery of nutrition via the gut triggers the release of gastrointestinal neuropeptides necessary for maintenance of the mucosal immune system.

Administration, Intranasal↗
PubMed2001

Impairment of mucosal immunity by parenteral nutrition: depressed nasotracheal influenza-specific secretory IgA levels and transport in parenterally fed mice.

OBJECTIVE: To examine the effects on mucosal selective transport of polymeric IgA (pIgA) and the ability of exogenous pIgA to provide protection despite altered mucosal transport. SUMMARY BACKGROUND DATA: Parenteral nutrition significantly impairs established antipseudomonal immunity and IgA-mediated antiviral immunity in association with gut-associated lymphoid tissue mass atrophy. Lack of enteral feeding also induces mucosal effects. METHODS: After immunization, nasotracheal levels of influenza-specific IgA were measured in cannulated mice randomized to chow feeding or parenteral nutrition. Nonimmune animals were randomized to chow or total parenteral nutrition, and after 5 days of diet were given a mixture of two antiinfluenza monoclonal antibodies, pIgA and IgG. Four hours after injection, nasal washes were collected and influenza-specific antibody levels were determined by enzyme-linked immunosorbent assay to calculate the selective transport index of IgA relative to IgG. In the final experiment, immunized animals were randomized to chow or parenteral feeding, and after 5 days, parenterally fed animals received either normal mouse serum or antiviral pIgA before viral challenge. Viral shedding was measured at 42 hours after challenge. RESULTS: Parenteral nutrition significantly reduced virus-specific IgA in nasotracheal washes. Parenteral nutrition depressed the selective transport index, demonstrating impaired mucosal transport of pIgA. Parenterally fed animals given specific antiviral pIgA but not normal mouse serum eliminated virus from the airway and regained mucosal protection, demonstrating adequate residual transport for immunity if adequate pIgA is present. CONCLUSION: Although both decreased IgA production due to gut-associated lymphoid tissue atrophy and impaired mucosal transport occur when enteral feeding is not provided, residual transport can provide antiviral protection if exogenous antiviral pIgA is available. Production, rather than transport, may be the most important factor in maintaining established respiratory tract IgA-mediated immunity.

Analysis of Variance↗
PubMed2001

Enteral nutrition prevents remote organ injury and death after a gut ischemic insult.

OBJECTIVE: To determine whether parenteral feeding (IV-TPN) influences the local and systemic response to an intestinal insult. SUMMARY BACKGROUND DATA: Parenteral feeding increases ICAM-1 expression and attracts neutrophils (PMNs) to the intestine compared with enterally fed animals. Because the gut is a priming bed for PMNs, the authors hypothesized that IV-TPN may affect organ injury after gut ischemia-reperfusion (I/R). METHODS: Mice were randomized to chow, IV-TPN, intragastric TPN, or complex enteral diet for 5 days' feeding. In experiment 1, 162 mice underwent 15 or 30 minutes of gut I/R, and death was recorded at 72 hours. In experiment 2, 43 mice underwent 15 minutes of gut ischemia and permeability was measured by 125I-labeled albumin at 3 hours after reperfusion. Lung PMN accumulation was measured by myeloperoxidase assay. In experiment 3, albumin leak was tested in the complex enteral diet group (n = 5) and the intragastric TPN group (n = 5) after 30 minutes of gut ischemia and 1 hour of reperfusion. RESULTS: In experiment 1, enteral feeding significantly reduced the death rate compared with IV-TPN after 15 minutes of I/R. After 30 minutes of gut ischemia, the IV-TPN and intragastric TPN groups showed a higher death rate than the chow and enteral diet groups. In experiment 2, IV-TPN significantly increased pulmonary and hepatic 125I albumin leak compared with enteral feeding without increasing pulmonary myeloperoxidase levels. In experiment 3, there were no differences in 125I albumin leak between the complex enteral diet and intragastric TPN groups. CONCLUSION: Enteral feeding reduced the death rate and organ permeability after 15 minutes of ischemia. However, prolonged ischemia (30 minutes) eliminated any benefits of intragastric TPN on survival.

Animals↗
PubMed2001

Modulation of organ ICAM-1 expression during IV-TPN with glutamine and bombesin.

The gut primes neutrophils (PMNs) during injury, which can then induce distant organ damage after a second insult. ICAM-1 is an important adhesion molecule in PMN attachment to the vascular endothelium. Parenteral nutrition (TPN) decreases gut levels of interleukin (IL)-4 and IL-10, two cytokines that are normal inhibitors of ICAM-1 expression. TPN also increases gut ICAM-1 expression and PMN accumulation. Since glutamine (GLN) and bombesin (BBS) prevent TPN-associated impairment of mucosal immunity, we hypothesized that GLN and BBS would modulate organ ICAM-1 expression in association with normalization of IL-4 and IL-10 levels. Forty-four mice were fed chow, TPN, or GLN-TPN (isonitrogenous 2% GLN-enriched TPN). After 5 days of diets, ICAM-1 expression was quantified in organs using the dual radiolabeled monoclonal antibody technique. In the next experiment, 29 mice were fed chow, TPN, or BBS-TPN (BBS 15 microg/kg TID) for 5 days to measure organ ICAM-1 expression. Total IL-4 and IL-10 levels were measured with ELISA from intestinal homogenates of another set of 52 mice fed chow, TPN, GLN-TPN, or BBS-TPN. TPN significantly increased ICAM-1 expression in the lung, kidney, and intestine compared with chow mice. GLN-TPN decreased intestinal, but not lung, ICAM-1 expression, while BBS-TPN reduced pulmonary, but not gut, ICAM-1 levels. GLN- and BBS-TPN returned gut IL-4 levels to normal, but failed to increase IL-10 levels. GLN and BBS had different effects on organ ICAM-1 expression induced by lack of enteral nutrition. Mechanisms other than recovery of IL-4 alone may be responsible for gut ICAM-1 expression.

Animals↗
PubMed2001

TPN decreases IL-4 and IL-10 mRNA expression in lipopolysaccharide stimulated intestinal lamina propria cells but glutamine supplementation preserves the expression.

Total parenteral nutrition (TPN) decreases intestinal IgA and levels of Th2 cytokines, interleukin (IL)-4, and IL-10 within the supernatants of intestinal homogenates. These cytokines are known to stimulate IgA production in vitro by cells of the gut-associated lymphoid tissue (GALT). Glutamine (GLN) supplementation of TPN normalizes GALT mass and cytokine levels. Because intestinal homogenates contain mucosa which itself is a source of cytokines, it was unclear whether cytokines change within the GALT itself. This study investigates dietary effects on IL-4 and IL-10 cytokine mRNA expression within isolated GALT lamina propria cells after lipopolysaccharide (LPS) stimulation. Prospective randomized experimental trials were used in this study. Fifty-nine mice were randomized to chow, intravenous TPN (IV-TPN), intragastric TPN (IG-TPN), complex enteral diet (CED), or 2% GLN-supplemented TPN (GLN-TPN). In experiment 1, animals were fed chow, IV-TPN, IG-TPN, or CED for 5 days and received intraperitoneal LPS (100 microg/kg BW), and then were sacrificed 1 h later. Intestine was harvested for GALT lamina propria. Total RNA was extracted from lamina propria cells and cytokine mRNA for IL-4, and IL-10 was measured by reverse transcriptase polymerase chain reaction. IgA levels of intestinal washing were also measured with ELISA. In experiment 2, mRNA for IL-4 and IL-10, and intestinal IgA levels were measured in mice fed chow, IV-TPN, or GLN-TPN as in experiment 1. Both IL-4 and IL-10 mRNA expression decreased significantly in IV-TPN mice compared to chow or CED feeding. IG-TPN resulted in IL-10 mRNA expression significantly lower than chow or CED but significantly better than IV-TPN. GLN preserved IL-4 and IL-10 mRNA levels, which correlated with intestinal IgA levels. Route and type of nutrition as well as GLN influence message for the Th2 type IgA-stimulating cytokines, IL-4 and IL-10, within the primary site of GALT IgA production, the lamina propria.

Animal Feed↗
PubMed2000

Increased expression of intestinal P-selectin and pulmonary E-selectin during intravenous total parenteral nutrition.

HYPOTHESIS: Intravenous total parenteral nutrition (TPN) induces intestinal polymorphonuclear neutrophil recruitment with increased intestinal intercellular adhesion molecule-1 expression. While intercellular adhesion molecule-1 causes firm adhesion of leukocytes to the endothelial cells, P- and E-selectin mediate leukocyte recruitment via rolling. Therefore, manipulation of nutrition may also affect P- and E-selectin expression in organs. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Male mice. INTERVENTIONS: Fifty-three mice were randomized to chow, intravenous TPN, or intragastric TPN. MAIN OUTCOME MEASURES: After 5 days of diet, mice were administered iodine 125-labeled anti-P-selectin antibody (or iodine 125-labeled anti-E-selectin antibody) and iodine 131-labeled nonbinding antibody to quantify P-selectin (or E-selectin) expression in organs (lung, liver, kidney, small intestine, colon, stomach, pancreas, mesentery, heart, and skeletal muscle). RESULTS: P-selectin in small intestine, colon, stomach, and pancreas in the intravenous TPN group increased significantly as compared with the chow and the intragastric TPN groups. E-selectin expression was up-regulated after intravenous TPN in the lung but not in other sites. CONCLUSIONS: In a time frame (5 days) when intercellular adhesion molecule-1 expression and neutrophil recruitment are increased, intestinal expression of P-selectin remains up-regulated. Early lung inflammatory changes are reflected by increases in E-selectin. This change may reflect early pulmonary dysfunction with intravenous TPN, but its significance requires further study.

Analysis of Variance↗
PubMed2000

Bombesin recovers gut-associated lymphoid tissue and preserves immunity to bacterial pneumonia in mice receiving total parenteral nutrition.

OBJECTIVE: To study the ability of bombesin (BBS) to recover gut-associated lymphoid tissue (GALT) and preserve immunity in a lethal model of Pseudomonas aeruginosa (Ps) pneumonia in mice receiving total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: TPN causes depression of mucosal immunity compared with enterally fed animals, which may explain the increased incidence of pneumonia in parenterally fed trauma patients. BBS prevents this TPN-induced GALT atrophy, depressed gastrointestinal and respiratory tract IgA levels, and impaired antiviral IgA-mediated mucosal immunity. The authors examined whether some supplement could be added to TPN to avoid this GALT atrophy and lower the incidence of infectious complications in the parenterally fed animal. METHODS: Male mice were randomized to chow or intravenous (IV) TPN. After 5 days of IV TPN, mice received 0, 1, 2, or 3 days of BBS IV three times a day and then were killed to harvest Peyer's patch, intraepithelium, and lamina propria for cell yields. Gastrointestinal and respiratory tract IgA levels were analyzed by enzyme-linked immunosorbent assay. Next, mice underwent intranasal inoculation with liposomes alone (nonimmune) or liposome-containing Ps polysaccharide. Ps immune mice were catheterized and randomized to chow, IV TPN, or IV TPN + BBS. The liposome group received chow but no IV catheter. These mice were given an LD90 dose of intratracheal Ps, and death rates were recorded. RESULTS: GALT and gastrointestinal and respiratory tract IgA levels improved to those in chow-fed mice after 3 days of BBS. Immunization reduced the death rate from 92% in chow-fed liposome-only animals to 20% in immunized animals. TPN-fed animals lost their mucosal immunity, with a death rate of 86% compared with 21% in the TPN + BBS group. CONCLUSION: The results demonstrate that BBS reverses TPN-induced changes in GALT and preserves mucosal immunity. Ps immunization reduces the death rate in a gram-negative pneumonia model and maintains gastrointestinal and respiratory immunity in Ps immune mice receiving IV TPN.

Animals↗
PubMed2000

Blunt hepatic injury: a paradigm shift from operative to nonoperative management in the 1990s.

OBJECTIVE: To analyze the outcome of hemodynamically stable patients with blunt hepatic injury managed nonoperatively, and to examine the impact of this approach on the outcome of all patients with blunt hepatic injury. SUMMARY BACKGROUND DATA: Until recently, operative management has been the standard for liver injury. A prospective trial from the authors' institution had shown that nonoperative management could safely be applied to hemodynamically stable patients with blunt hepatic injury. The present study reviewed the authors' institutional experience with blunt hepatic trauma since that trial and compared the results with prior institutional experience. METHODS: Six hundred sixty-one patients with blunt hepatic trauma during the 5-year period ending December 1998 were reviewed (NONOP2). The outcomes were compared with two previous studies from this institution: operative 1985 to 1990 (OP) and nonoperative 1993 to 1994 (NONOP1). RESULTS: All 168 OP patients were managed operatively. Twenty-four (18%) of 136 NONOP1 patients and 101 (15%) of the 661 NONOP2 patients required immediate exploration for hemodynamic instability. Forty-two (7%) patients failed nonoperative management; 20 were liver-related. Liver-related failures of nonoperative management were associated with higher-grade injuries and with larger amounts of hemoperitoneum on computed tomography scanning. Twenty-four-hour transfusions, abdominal infections, and hospital length of stay were all significantly lower in the NONOP1 and NONOP2 groups versus the OP cohort. The liver-related death rate was constant at 4% in the three cohorts over the three time periods. CONCLUSIONS: Although urgent surgery continues to be the standard for hemodynamically compromised patients with blunt hepatic trauma, there has been a paradigm shift in the management of hemodynamically stable patients. Approximately 85% of all patients with blunt hepatic trauma are stable. In this group, nonoperative management significantly improves outcomes over operative management in terms of decreased abdominal infections, decreased transfusions, and decreased lengths of hospital stay.

Abdominal Abscess↗
PubMed2000

Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebo-controlled, crossover study.

OBJECTIVE: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). DESIGN: A randomized, crossover study. SETTING: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. PATIENTS: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period. INTERVENTIONS: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. MEASUREMENTS AND MAIN RESULTS: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3+/-4.5 [SEM] mins and 10.9+/-5.8 vs. 30.1+/-4.5 mins, respectively [p<.05]). Metoclopramide (9.7+/-15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7+/-8.1 and 50.9+/-13.5 mins, respectively [p<.05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7+/-4.5 vs. 22.9+/-5.7 mins [p<.05]). CONCLUSION: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride.

Acetaminophen↗
PubMed2000

Nutritional and pharmacological enhancement of gut-associated lymphoid tissue.

There has been an explosion of research in the field of nutrition over the past quarter century. Clinical studies have demonstrated the effectiveness of providing nutrition by the enteral route in reducing septic morbidity in critically ill patients. These improved outcomes have been substantiated by animal models that show that enteral nutrition decreases gut permeability while maintaining the gut-associated lymphoid tissue (GALT) in mucosal immunity. Evidence points to the important immunological role of the gut in the maintenance of mucosal immunity at both intestinal and extraintestinal sites. The preservation of this mucosal immunity by enteral nutrition is consistent with the lower morbidity seen in severely injured patients who receive nutrition via the gastrointestinal tract. For patients who are unable to be fed by the enteral route and who require parenteral nutrition, several supplements show promise in enhancing the mucosal immune system defenses. The nutritional and pharmacological tactics that may enhance the GALT and thereby maintain mucosal immunity are examined.

Animals↗
PubMed1999

Glutamine-enriched total parenteral nutrition preserves respiratory immunity and improves survival to a Pseudomonas Pneumonia.

BACKGROUND: Addition of 2% glutamine (GLN), a specific lymphocyte fuel, prevents deleterious effects of TPN on gut-associated lymphoid tissue and IgA while preserving IgA-mediated upper respiratory immunity to influenza virus. We examined whether a 2% GLN-enhanced TPN solution preserves respiratory immunity to a lethal and clinically relevant pneumonia challenge. MATERIALS AND METHODS: Male ICR mice were randomized to chow (n = 20), TPN (n = 20), or an isonitrogenous, isocaloric TPN-2% GLN solution (n = 17). All groups were immunized 10 days before surgery with Pseudomonas polysaccharide-containing liposomes (LIP) to confer immunity except for a nonimmune chow-fed LIP control group (n = 21) which received LIP without Pseudomonas. Mice received 5 days of diet and then were given an LD90 dose of 1.2 x 10(8) intratracheal Pseudomonas bacteria, and mortality was recorded. RESULTS: Immunization reduced mortality compared with LIP alone. TPN impaired immunity and reduced survival while GLN maintained immunization effectiveness. CONCLUSIONS: Pseudomonas immunization reduces mortality to Pseudomonas pneumonia, but this immunity is lost with TPN. Addition of 2% GLN to TPN preserves immunity in the respiratory tract and reduces mortality to a lethal bacterial challenge compared with standard TPN.

Animals↗
PubMed1999

Route of nutrition influences intercellular adhesion molecule-1 expression and neutrophil accumulation in intestine.

HYPOTHESIS: The levels of intestinal interleukin 10 and interleukin 4, inhibitors of intercellular adhesion molecule-1 (ICAM-1) expression, decline with total parenteral nutrition (TPN). These cytokine changes induced by lack of enteral nutrition may increase ICAM-1 expression, resulting in polymorphonuclear neutrophil accumulation in intestine. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Male mice. INTERVENTIONS: Sixty-three mice were randomized to chow, intravenous TPN, or intragastric TPN. MAIN OUTCOME MEASURES: Experiment 1: After diet manipulation, iodine 125-labeled anti-ICAM-1 antibody and iodine 131-labeled nonbinding antibody were injected to quantify ICAM-1 expression on endothelial cells in the lung, liver, kidney, and small intestine. Measurement of myeloperoxidase was used to quantify polymorphonuclear neutrophil accumulation in the organs. Experiment 2: Intestine was harvested for both ICAM-1 and myeloperoxidase levels after chow refeeding of mice in the intravenous TPN group. RESULTS: In experiment 1, uninjured mice fed intravenous TPN showed significantly increased intestinal ICAM-1 expression and polymorphonuclear neutrophil accumulation with no significant changes in the lung, liver, or kidney. No changes occurred in mice fed chow or intragastric TPN. In experiment 2, reinstitution of enteral feeding returned intestinal ICAM-1 and myeloperoxidase levels to normal. CONCLUSION: Gut changes associated with lack of enteral feeding induce endothelial changes and an immunologic response, which may influence subsequent responses to injury.

Animals↗
PubMed1999

The gut's role in metabolism, mucosal barrier function, and gut immunology.

The gastrointestinal tract functions not only to absorb nutrients, it also plays an important immunologic role during health and critical illness. Under experimental and certain clinical conditions, stimulating the gut attentuates the stress response and avoids mucosal atrophy and increases permeability. Gut stimulation prevents atrophy of the gut-associated lymphoid tissue, the body's major defender of moist mucosal surfaces. A better understanding of gut function and improved nutrient delivery has clinical implications in the treatment of critically ill patients.

Animals↗
PubMed1999

Route and type of nutrition influence mucosal immunity to bacterial pneumonia.

OBJECTIVE: To develop a model of established respiratory immunity against Pseudomonas aeruginosa pneumonia and to investigate the effects of route and type of nutrition on this immunity. SUMMARY BACKGROUND DATA: Diet influences the ability of gut-associated lymphoid tissue (GALT) to maintain mucosal immunity. Complex enteral diets and chow maintain normal GALT populations against established IgA-mediated antiviral respiratory immunity. Both intravenous and intragastric total parenteral nutrition (TPN) produce GALT atrophy, but only intragastric TPN preserves established antiviral immunity. The authors hypothesized that both GALT-depleting diets (intragastric and intravenous TPN) would impair immunity against bacterial pneumonia. METHODS: P. aeruginosa was administered intratracheally to determine the mortality rate at increasing doses, and liposomes containing P. aeruginosa antigens were used to generate effective respiratory immunization. In the final experiment, mice received liposomes containing P. aeruginosa antigens to establish immunity and then were randomized to chow, complex enteral diets, intragastric TPN, or intravenous TPN. After 5 days of diet, mice received live intratracheal P. aeruginosa, and the death rate was recorded at 24 and 48 hours. RESULTS: The LD50 and LD100 were 9 x 10(7) and 12 x 10(7), respectively. Immunization reduced the mortality rate from 66% to 12%. This immunization was maintained in mice fed chow or a complex enteral diet and was lost in animals receiving intravenous TPN. Intragastric TPN partially preserved this respiratory immunity. CONCLUSIONS: Protection against bacterial pneumonia can be induced by prior antigenic immunization. This protection is lost with intravenous TPN, partially preserved with a chemically defined enteral diet, and completely preserved with chow or complex enteral diets. Both route and type of nutrition influence antibacterial respiratory tract immunity.

Animals↗
PubMed1999

Route and type of nutrition influence IgA-mediating intestinal cytokines.

OBJECTIVE: To examine the levels of a Th1 IgA-inhibiting cytokine (interferon gamma) and the Th2 IgA-stimulating cytokines (interleukin [IL]-4, IL-5, IL-6, and IL-10) within the intestine of animals manipulated with enteral or parenteral nutrition, and to correlate these cytokine alterations with intestinal IgA levels. SUMMARY BACKGROUND DATA: Enteral feeding significantly reduces the incidence of pneumonia in critically injured patients compared with intravenous total parenteral nutrition (IV TPN) or no nutritional support. Experimentally, complex diets prevent impairments in mucosal immunity induced by IV TPN. These impairments include decreases in intestinal and respiratory tract IgA levels, impaired IgA-mediated antiviral defenses, and increases in the mortality rate against established immunity to Pseudomonas pneumonia. Intragastric (IG) TPN maintains antiviral defenses but only partially preserves protection against Pseudomonas pneumonia. Because IgA levels depend on interactions between Th1 IgA-inhibiting and Th2 IgA-stimulating cytokines, the authors postulated differences in gut cytokine balance in enterally and parenterally fed mice. METHODS: Sixty-one mice were randomized to receive chow, IV TPN, IG TPN, or an isocaloric, complex enteral diet. After 5 days of feeding, animals were killed and supernatants from samples of intestine were harvested, homogenized, and assayed for Th1 and Th2 cytokines by enzyme-linked immunosorbent assay. RESULTS: The Th2 cytokines, IL-5 and IL-6, and the Th1 cytokine, interferon gamma, remained unchanged by diet. IL-4 levels decreased significantly in both IV and IG TPN groups versus the chow or complex enteral diet groups, whereas IL-10 decreased only in IV TPN mice. Decreases in Th2 cytokines correlated with intestinal IgA levels. CONCLUSION: Chow and complex enteral diets maintain a normal balance between IgA-stimulating and IgA-inhibiting cytokines while preserving normal antibacterial and antiviral immunity. The IgA-stimulating cytokine IL-4 drops significantly in mice receiving IG and IV TPN in association with reduced IgA levels, whereas IL-10 decreases significantly only in mice receiving IV TPN. These data are consistent with severely impaired mucosal immunity with IV TPN and partial impairment with IG TPN and provide a cytokine-mediated explanation for reduction in diet-induced mucosal immunity.

Animals↗
PubMed1998

Nutritional support and infection: does the route matter?

Questions regarding the effects of the route of nutrition began to surface shortly after the introduction of total parenteral nutrition (TPN). Although TPN has become a life-saving therapy for patients who cannot tolerate enteral nutrition, it is not the panacea it was hoped to be. It appears that the enteral route of nutrition decreases rates of infectious complications compared with parenteral feeding. Reasons for this phenomenon are not clear, but it seems that enteral nutrition supports the gut barrier and gut-associated lymphoid tissue, which may have effects on infections at distant sites such as the lung. These effects do not appear to be due solely to prevention to malnutrition, as the infectious complications develop early after injury or illness. However, the lack of understanding of the mechanisms does not negate the fact that in many clinical studies the enteral route of nutrition is superior to the parenteral route in terms of reducing infectious complications in critically ill or injured patients.

Animals↗