The Effect of Glutamine on Systemic Inflammation During Human Experimental Endotoxemia

Study Overview
=================
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.

Official Title
-----------------
The Effect of Glutamine Infusion on the Inflammatory Response and HSP-70 in BMNCs During Human Experimental

Conditions
-----------------
Sepsis, Systemic Inflammation

Intervention / Treatment
-----------------
* Dietary Supplement: alanine-glutamine infusion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy young males Exclusion Criteria: Any kind of acute or chronic diseases

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Dietary Supplement: alanine-glutamine infusion<br> <br> |
| Placebo Comparator: 2<br> | Dietary Supplement: alanine-glutamine infusion<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma-levels of cytokines |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat shock protein -70 production from BMNCs |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
glutamine inflammation HSP70 sepsis