Glutamine attenuates tumor necrosis factor-alpha release and enhances heat shock protein 72 in human peripheral blood mononuclear cells.
OBJECTIVE
Overexpression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) can contribute to multiple organ dysfunction syndrome and septic shock in critically ill patients. We previously found that glutamine (GLN) can attenuate cytokine expression, induce heat shock protein 72 (HSP 72), and protect against endotoxin-induced mortality and organ injury in an in vivo rat model. However, data on the effect of GLN on direct attenuation of cytokine release and HSP 72 expression in human peripheral blood polymorphonuclear cells (PBMCs) is lacking.


METHODS
In this study, we assessed the effect of GLN on TNF-alpha and HSP 72 expression in human PBMCs. After treating with various doses of GLN, human PBMCs were stimulated with lipopolysaccharide (LPS). TNF-alpha release was analyzed via enzyme-linked immunosorbent assay and HSP 72 via western blot.


RESULTS
GLN at doses greater than 4 mM decreased TNF-alpha release at 4 and 24 h after LPS stimulation. Sublethal heating of PBMCs before LPS also markedly decreased TNF-alpha after LPS. Doses of GLN greater than 2 to 4 mM led to an increase in HSP 72 expression after LPS.


CONCLUSIONS
These results indicate that GLN, which may improve outcomes in critically ill patients, can directly attenuate pro-inflammatory cytokine release in PBMCs. This effect may be related to enhanced HSP 72 expression.
Wischmeyer
Paul E
PE
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. paul.wischmeyer@uchsc.edu
Riehm
Jacob
J
Singleton
Kristen D
KD
Ren
Hongyu
H
Musch
Mark W
MW
Kahana
Madelyn
M
Chang
Eugene B
EB
D015153:Blotting, Western; D002478:Cells, Cultured; D016638:Critical Illness; D016207:Cytokines / Q000378:metabolism; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005973:Glutamine / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009102:Multiple Organ Failure / Q000503:physiopathology / Q000517:prevention & control; D012772:Shock, Septic / Q000503:physiopathology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016207:Cytokines; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine