Original ArticlesGlutamine-Supplemented Total Parenteral Nutrition Reduces Blood Mononuclear Cell Interleukin-8 Release in Severe Acute Pancreatitis
Introduction
Glutamine is the most abundant amino acid both in the plasma and in the intracellular free amino acid pool.[1]It is essential for a wide variety of physiologic processes, in particular, the growth and function of immune cells including lymphocytes and macrophages.[2]Glutamine is normally synthesized de novo by a number of cells, and, therefore, is not an essential amino acid. However, in conditions of excess glutamine utilization, such as sepsis, trauma, major surgery, or severe acute pancreatitis, endogenous glutamine production may not be adequate, and glutamine depletion occurs.[3]Exogenous glutamine may be required to satisfy the body’s glutamine requirements, but the glutamine depletion is compounded by the fact that many of these patients are being fed parenterally rather than enterally, and traditional parenteral feeding does not contain glutamine. This is because of its relative insolubility as well as its long-term instability in solution during heat sterilization and long-term storage where it may degrade to ammonia and pyroglutamic acid.
Patients with severe acute pancreatitis can develop local pancreatic complications related to pancreatic necrosis and develop distant organ dysfunction.[4]Infection of the necrotic pancreas is thought to be a key step in the progression to a persistent systemic inflammatory response and multiple organ dysfunction.[5]An intact T-cell response plays a cental role in the defense of the host against bacterial invasion, and T-cell DNA synthesis (as determined by thymidine incorporation in vitro) correlates well with host resistance to sepsis in vivo.[6]T-cells are dependent on glutamine for optimal growth and function,[7]and glutamine depletion may be partly responsible for T-cell suppression seen in these severely stressed patients.[8]T-cells also exert an important regulatory role on monocyte proinflammatory cytokine release,9, 10and T-cell suppression may contribute to the prolonged increase in proinflammatory cytokine release (interleukin [IL]-6 and interleukin-8) observed in patients with severe acute pancreatitis.11, 12Clinical susceptibility to sepsis may also be enhanced by abnormal production of proinflammatory cytokines.[13]
Recently, the development of glutamine dipeptides has allowed glutamine to be introduced into total parenteral nutrition (TPN) regimens that are stored prior to administration to patients. These dipeptides are stable in solution but are rapidly broken down in vivo to allow immediate bioavailability of the constitutent amino acids. The clinical administration of these compounds is well tolerated, even in patients with severe sepsis.[14]The aims of this study were to perform a double-blind randomized controlled study comparing the effect of glutamine-supplemented total parenteral nutrition versus conventional total parenteral nutrition on T-cell proliferative response and proinflammatory cytokine release (tumor necrosis factor, IL-6, and IL-8) by peripheral blood mononuclear cells in patients with severe acute pancreatitis.
Section snippets
Patients
Patients over the age of 18 y with severe acute pancreatitis were included in the study. Severe acute pancreatitis for the purpose of this study was defined as a modified Glasgow score[15]of 3 or more in a patient requiring TPN because of persistent failure of the gastrointestinal tract 7 d after the onset of illness. Patients with respiratory failure (requiring ventilatory support), renal failure (creatinine > 200 μmol/L) or hepatic failure (bilirubin >100 μmol/L in the absence of
Results
Fourteen patients with severe acute pancreatitis were recruited to the study, 7 in each group. One patient in the glutamine- supplemented TPN group was withdrawn as a result of central line sepsis on day 3 of the study protocol and was excluded from additional analysis or comparison. The patients characteristics at entry to the study are shown in Table I. The etiology of the acute pancreatitis in the glutamine TPN group was gallstones in 2 patients, alcohol in 1 patient, idiopathic in 2
Discussion
Patients with severe acute pancreatitis are recognized to suffer from glutamine depletion, and the development of sepsis within the necrotic pancreas and at distant sites may adversely affect survival of the patient. Glutamine depletion has been implicated in the development of T-cell suppression seen in such patients. This study has shown that the administration of total parenteral nutrition supplemented with glutamine (as the glycyl-glutamine dipeptide) tends to improve T-cell DNA synthesis
Acknowledgements
Research support received from Pharmacia and Upjohn.
References (25)
- et al.
Bacterial contamination of pancreatic necrosis
Gastroenterology
(1986) Glutamine and glucose metabolism in human peripheral lymphocytes
Metabolism
(1988)- et al.
The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection
J Surg Res
(1990) - et al.
Glutamine and macrophage function
Metabolism
(1992) - et al.
Interleukin-8 and the development of adult respiratory distress syndrome in at-risk groups
Lancet
(1993) - et al.
Glutamine
Br J Surg
(1996) Immunoenhancement via enteral nutrition
Arch Surg
(1993)- et al.
Is glutamine a conditionally essential amino acid
Nutr Rev
(1990) A clinically based classification for acute pancreatitis
Arch Surg
(1993)- et al.
Temporal correlation of impaired immune response after thermal injury with susceptibility to infection in a murine model
Surgery
(1988)
Immune function early in acute pancreatitis
Br J Surg
Interleukin-4 down regulates interleukin-6 production in human peripheral blood mononuclear cells
J Leukoc Biol
Cited by (143)
Antioxidants as a treatment for acute pancreatitis: A meta-analysis
2015, PancreatologyCitation Excerpt :We found a non-significant positive effect of antioxidants on mortality in patients with AP (RR 0.66; 95%CI 0.30–1.46; I2 = 21%) (Fig. 3) [11,16,22–30]. Glutamine was investigated in 5 studies, with 3 studies assessing hospital stay [11,22,25], 4 assessing complications [11,22,25,28] and all 5 studies assessing mortality rates [11,16,22,25,28]. The effect of glutamine on hospital stay was non-significant (MD −1.72; 95%CI −4.53 to 1.08; I2 = 27%).
Parenteral immunonutrition in patients with acute pancreatitis: A systematic review and meta-analysis
2015, Clinical NutritionCitation Excerpt :Cumulative meta-analysis suggested that the relative risk of mortality has been declined by the late of 1998 (Supplementary data, Fig. S2). Five records [31–35] (196 participants) among 7 studies had data on LOS for analysis; and 2 studies (De Beaux et al. and Wang et al.) [30,36] did not published information in this field. As represented in Fig. 4, parenteral immunonutrition was significantly associated with reduction in hospitalization in acute pancreatitis (MD = −2.93 days; 95% CI, –4.70 to −1.15; p ≤ 0.001).