Parenteral glutamine increases serum heat shock protein 70 in critically ill patients
- 432 Downloads
Heat shock protein 70 (HSP-70) is protective against cellular and tissue injury. Increased serum HSP-70 levels are associated with decreased mortality in trauma patients. Glutamine (Gln) administration increases serum and tissue HSP-70 expression in experimental models of sepsis. Gln has been safely administered to critically ill patients and can improve clinical outcomes, but the effect of Gln administration on HSP-70 expression in humans is unknown. We examined whether Gln-supplemented parenteral nutrition (PN) increases serum HSP-70 levels in critically ill patients.
Design and setting
Randomized, controlled, double-blind study in surgical intensive care units (SICU) in a university hospital.
29 patients admitted to the SICU and requiring PN for more than 7 days.
Patients received either Gln-PN (containing alanyl-glutamine dipeptide; 0.5 g/kg per day; n=15) or standard Gln-free PN (control-PN) that was iso-nitrogenous to Gln-PN (n=14). Serum HSP-70 concentrations were measured at enrollment and at 7 days. Clinical outcome measures were also determined.
HSP-70 concentrations were unchanged in control-PN subjects from baseline to day 7. In marked contrast, Gln-PN subjects demonstrated significantly higher (3.7-fold) serum HSP-70 concentrations than control subjects. In Gln-PN patients there was a significant correlation between increases in HSP-70 levels over baseline and decrease in ICU length of stay.
Gln-PN significantly increases serum HSP-70 in critically ill patients. The magnitude of HSP-70 enhancement in Gln-treated patients was correlated with improved clinical outcomes. These data indicate the need for larger, randomized trials of the Gln effect on serum and tissue HSP-70 expression in critical illness and relationship to clinical outcomes.
KeywordsHeat shock proteins Critical Illness Glutamine Parenteral nutrition Outcome
- 2.De Maio A (1999) Heat shock proteins: facts, thoughts, and dreams. Shock 11:1–12Google Scholar
- 9.Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M (2001) Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 29:2075–2080CrossRefPubMedGoogle Scholar
- 10.Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R, Morrow FD, Jacobs DO, Smith RJ, Antin JH, et al (1992) Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann Intern Med 116:821–828PubMedGoogle Scholar
- 13.Wischmeyer PE, Musch MW, Madonna MB, Thisted R, Chang EB (1997) Glutamine protects intestinal epithelial cells: role of inducible HSP70. Am J Physiol 272:G879–G884Google Scholar
- 15.Wischmeyer PE, Kahana M, Wolfson R, Ren H, Musch MM, Chang EB (2001) Glutamine induces heat shock protein and protects against endotoxin shock in the rat. J Appl Physiol 90:2403–2410Google Scholar
- 16.Wischmeyer PS, Serkova KN (2004) Glutamine attenuates multiple pathways of sepsis-induced injury and improves survival following peritonitis: role of heat stress protein pathway manipulation. Presented at Society for Critical Care MedicineGoogle Scholar
- 28.Houdijk AP, Rijnsburger ER, Jansen J, Wesdorp RI, Weiss JK, McCamish MA, Teerlink T, Meuwissen SG, Haarman HJ, Thijs LG, van Leeuwen PA (1998) Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352:772–776CrossRefPubMedGoogle Scholar
- 29.Wischmeyer PE, Singleton KD (2003) Post-treatment with single dose of glutamine attenuates IL-18 expression and reduces polymicrobial sepsis-induced mortality. Crit Care Med 31:A11Google Scholar