Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia

Paul E. Wischmeyer, Madelyn Kahana, Rachel Wolfson, Hongyu Ren, Mark M. Musch, Eugene B. Chang

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Clinical trials have demonstrated that glutamine (GLN) supplementation can decrease infectious morbidity and improve survival in a number of settings of critical illness. The mechanism of this protection remains unclear. The objective of this study was to evaluate the effect of GLN on cytokine release, organ injury, and survival from endotoxin-induced septic shock. Endotoxemia was induced in Male Sprague-Dawley rats by intravenous administration of 5mg/kg Escherichia coli lipopolysaccharide (LPS). Concomitantly, animals were fluid resuscitated with a lactated ringers (LR) solution and given GLN (0.75 g/kg IV) or LR alone. Blood samples were obtained at multiple time points post-LPS injury for cytokine analysis. Survival rates were monitored for 72 h. Organ injury was evaluated in a separate set of animals via pathologic exam of tissues harvested 6 h post-LPS injury. A single dose of GLN significantly attenuated the release of TNF-α at 2 h (P < 0.005) and IL-1β at 4 h (P < 0.0001). This attenuation of cytokine release was associated with a significant decrease in mortality (P < 0.003). Pathologic exam demonstrated significant protection of both lung and small bowel tissue by GLN. Blood gas values 6-h post-LPS injury showed increased PaO2 and bicarbonate concentration in GLN treated animals. These data indicate that GLN can significantly attenuate pro-inflammatory cytokine release, protect against end-organ damage, and decrease mortality from endotoxemia. GLN confers protection even when administered at the onset of endotoxemia, rather then as pre-treatment. Thus, one explanation for the clinical benefits observed from GLN-supplementation may be related to the attenuation of pro-inflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)398-402
Number of pages5
JournalShock
Volume16
Issue number5
StatePublished - Nov 2001
Externally publishedYes

Fingerprint

Endotoxemia
Glutamine
Cytokines
Mortality
Lipopolysaccharides
Wounds and Injuries
Tissue Survival
Bicarbonates
Septic Shock
Interleukin-1
Critical Illness
Endotoxins
Intravenous Administration
Sprague Dawley Rats
Survival Rate
Gases
Clinical Trials
Escherichia coli
Morbidity
Lung

Keywords

  • Amino acid
  • Animal model
  • Interleukin-1β
  • Lipopolysaccharide
  • Septic shock
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Wischmeyer, P. E., Kahana, M., Wolfson, R., Ren, H., Musch, M. M., & Chang, E. B. (2001). Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia. Shock, 16(5), 398-402.

Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia. / Wischmeyer, Paul E.; Kahana, Madelyn; Wolfson, Rachel; Ren, Hongyu; Musch, Mark M.; Chang, Eugene B.

In: Shock, Vol. 16, No. 5, 11.2001, p. 398-402.

Research output: Contribution to journalArticle

Wischmeyer, PE, Kahana, M, Wolfson, R, Ren, H, Musch, MM & Chang, EB 2001, 'Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia', Shock, vol. 16, no. 5, pp. 398-402.
Wischmeyer PE, Kahana M, Wolfson R, Ren H, Musch MM, Chang EB. Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia. Shock. 2001 Nov;16(5):398-402.
Wischmeyer, Paul E. ; Kahana, Madelyn ; Wolfson, Rachel ; Ren, Hongyu ; Musch, Mark M. ; Chang, Eugene B. / Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia. In: Shock. 2001 ; Vol. 16, No. 5. pp. 398-402.
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