Hyperosmotic stress enhances cytokine production and decreases phagocytosis in vitro.
BACKGROUND
Hyperglycemia is associated with negative outcomes in various settings of critical illness; infectious complications, especially, seem to be increased. On the other hand, intensive insulin therapy (IIT) has been shown to improve outcome in clinical trials. Whether normoglycemia itself or the application of insulin is responsible for the observed findings is unknown. We therefore tested the effect of glucose and insulin on various immune functions in vitro.


METHODS
Human peripheral blood mononuclear cells (PBMCs) were incubated ex vivo with low doses of lipopolysaccharide (LPS). PBMCs were incubated with various osmotic agents, insulin, or a combination of both. Interleukin (IL)-6 and IL-1 cytokine response was measured by enzyme-linked immunosorbent assay. In addition, we investigated the effects of glucose on phagocytosis and oxidative burst in human granulocytes.


RESULTS
Increasing concentrations of both glucose and mannitol significantly enhanced LPS-induced cytokine production. Insulin alone did not alter cytokine production and had only a minor influence in combination with glucose. Phagocytosis and oxidative burst were significantly reduced with increasing concentrations of glucose and mannitol.


CONCLUSIONS
Hyperglycemia may lead to inflammation by enhancing cytokine production via the direct effects of hyperosmotic stress. Impaired phagocytosis and oxidative burst under hyperglycemia may weaken defense mechanisms of the host. Our in vitro findings may help to explain the beneficial effects of IIT not only in diabetic but also in critically ill patients.
Otto
Natalie M
NM
Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.
Schindler
Ralf
R
Lun
Andreas
A
Boenisch
Olaf
O
Frei
Ulrich
U
Oppert
Michael
M
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009995:Osmosis / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D016207:Cytokines; D007328:Insulin; D005947:Glucose