Clinical trial NCT00780520: The Effect of Glutamine on Systemic Inflammation During Human Experimental Endotoxemia
Official title: The Effect of Glutamine Infusion on the Inflammatory Response and HSP-70 in BMNCs During Human Experimental
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Systemic Inflammation
Keywords: glutamine inflammation HSP70 sepsis
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2008-10-27
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Healthy young males

Exclusion Criteria:

* Any kind of acute or chronic diseases

Primary outcomes:
measure: Plasma-levels of cytokines
Secondary outcomes:
measure: Heat shock protein -70 production from BMNCs
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Centre of Inflammation and Metabolism, Rigshospitalet
Study officials:
References:
citation: Andreasen AS, Pedersen-Skovsgaard T, Mortensen OH, van Hall G, Moseley PL, Pedersen BK. The effect of glutamine infusion on the inflammatory response and HSP70 during human experimental endotoxaemia. Crit Care. 2009;13(1):R7. doi: 10.1186/cc7696. Epub 2009 Jan 27.