Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide.
BACKGROUND
Ketamine has been reported to exert anti-inflammatory effects on macrophages stimulated with lipopolysaccharide (LPS) in vitro and in vivo. Several studies have reported conflicting results regarding the effects of propofol on cytokine production from immune cells. However, there have been no reports of the effects of these agents on inflammatory responses in glial cells. We investigated the effects of ketamine and propofol on LPS-induced production of nitric oxide, tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) from primary cultures of rat glial cells in vitro.


METHODS
Glial cells were stimulated with LPS in the absence and presence of various concentrations of ketamine (30-1000 microM) or propofol (30 and 300 microM). Nitric oxide released into the culture media was determined by measuring nitrite using the Griess reaction, and concentrations of TNF-alpha and PGE(2) were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Ketamine reduced LPS-induced TNF-alpha production without significant inhibition of nitrite release in mixed glial cells, astrocyte cultures and microglial cultures. Ketamine also inhibited LPS-induced production of PGE(2) in astrocyte cultures. In contrast, propofol had no effect on LPS-induced nitrite or TNF-alpha production in mixed glial cells.


CONCLUSIONS
The data demonstrate that ketamine inhibited some of the inflammatory responses of both astrocytes and microglial cells treated with LPS without causing major change in nitric oxide release. Propofol had no effect on the production of nitric oxide or TNF-alpha from LPS-stimulated glial cells.
Shibakawa
Y Saito
YS
Departments of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Sasaki
Y
Y
Goshima
Y
Y
Echigo
N
N
Kamiya
Y
Y
Kurahashi
K
K
Yamada
Y
Y
Andoh
T
T
D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007649:Ketamine; D015232:Dinoprostone; D015742:Propofol