Propofol inhibits human neutrophil functions.
Neutrophils play important roles in the antibacterial host defense mechanism and in the pathogenesis of tissue injury. Propofol has been reported to impair the production of reactive oxygen species from neutrophils. We examined the effect of propofol (2,6-diisopropylphenol), at clinically relevant concentrations and at 10 and 100 times this concentration, on several aspects of human neutrophil functions using an in vitro system. Propofol significantly inhibited chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, propofol suppressed these neutrophil functions, but it did not decrease ROS generation by the cell-free (xanthine-xanthine oxidase) system. Increase in intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine was dose-dependently attenuated by propofol. This decreasing effect on [Ca2+]i in neutrophils may represent one of the mechanisms responsible for the inhibition of neutrophil functions by propofol.


CONCLUSIONS
Neutrophils play a pivotal role in the antibacterial host defense system and tissue injury. We found that at clinically relevant concentrations, propofol impaired neutrophil functions. Further studies may determine whether this impairment, observed in vitro, leads to clinical immunological suppression.
Mikawa
K
K
Department of Anaesthesiology, Kobe University School of Medicine, Japan.
Akamatsu
H
H
Nishina
K
K
Shiga
M
M
Maekawa
N
N
Obara
H
H
Niwa
Y
Y
D018681:Anesthetics, General / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D018681:Anesthetics, General; D005609:Free Radicals; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D015742:Propofol