The Effect of Glutamine on Systemic Inflammation During Human Experimental Endotoxemia
Glutamine levels decrease during severe sepsis; this may be associated with increased mortality. The investigators tested the effects of glutamine supplementation on systemic inflammation in a human sepsis model.
The investigators found that glutamine levels drops significantly during experimentally induced systemic inflammation. However, glutamine did not affect the degree of inflammation.
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
|Official Title:||The Effect of Glutamine Infusion on the Inflammatory Response and HSP-70 in BMNCs During Human Experimental|
- Plasma-levels of cytokines [ Designated as safety issue: No ]
- Heat shock protein -70 production from BMNCs [ Designated as safety issue: No ]
|Study Start Date:||June 2007|
|Study Completion Date:||October 2007|
|Primary Completion Date:||October 2007 (Final data collection date for primary outcome measure)|
|Experimental: 1||Dietary Supplement: alanine-glutamine infusion|
|Placebo Comparator: 2||Dietary Supplement: alanine-glutamine infusion|
Glutamine levels have been shown to decrease substantially with severe sepsis and this has been connected with increased mortality. Therefore, in the present study, we infused either saline or Alanine-glutamine during an endotoxin challenge and measured parameters related to an immune response, i.e. plasma cytokines and Heat Shock Protein (HSP)-70.
Materials and Methods This was a double blind, randomised, placebo-controlled crossover trial in eight healthy young men. The study was performed in random order on two separate days, with a four-week washout period between days. Subjects received an infusion of Alanine-glutamine ( Dipeptiven) at a rate of 0.025 g / (kg BW * h) for 10 hrs or saline. After two hours of infusion subjects received an intravenous bolus of E. coli endotoxin (0.3 ng/kg). Blood samples were collected hourly for the following eight hours. HSP-70 protein content in isolated Blood Mononuclear Cells (BMNCs) was measured by western blotting.
Results and Discussion Plasma glutamine was significantly increased during infusion with alanine-glutamine infusion. En-dotoxin caused a reduction in plasma-glutamine during saline infusion as well as during Alanine-glutamine infusion. A significant effect of endotoxin was found on leukocyte subpopulations, tumor necrosis factor-a, interleukin-6, the expression of HSP-70 in BMNCs, temperature, and heart rate. However, no differences were detected between treatments with regard to the effect of endotoxin on any of these parameters.
Conclusion Endotoxemia reduces plasma glutamine independently of parenteral infusion of alanine-glutamine. Glutamine does not alter the response of leukocytes, leukocyte subpopulations, IL-6, or TNF-α, or the expression of HSP-70 in BMNCs to endotoxemia.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00780520
|Centre of Inflammation and Metabolism, Rigshospitalet|
|Copenhagen, Denmark, DK-2100|