Inhibitory Effects of Pentobarbital and Phenobarbital on Human Neutrophil Functions

Abstract

Neutrophils are important components of the immune system which protects the host from bacterial invasion. Phenobarbital and pentobarbital are used to treat seizures/convulsions in critically ill patients who are sometimes immunocompromised hosts. In the current study we examined the effect of pentobarbital and phenobarbital at clinically relevant concentrations and at 10 and 100 times these concentrations on several aspects of human neutrophil functions using ex vivo system. The two barbiturates impaired neutrophil chemotaxis but failed to suppress phagocytosis. Pentobarbital and phenobarbital also inhibited production of superoxide (O2), hydrogen peroxide (H2O2), and hydroxyl radical (OH·) by neutrophils in a dose-dependent manner. These drugs did not scavenge the reactive oxygen species (ROS) generated by the xanthine-xanthine oxidase system. Elevation of intracellular calcium concentrations ([Ca2+]i) in neutrophils by a stimulant was dose-dependently attenuated with pentobarbital and phenobarbital. The two anesthetics also decreased protein kinase C (PKC) activity. These effects on [Ca2+]i and PKC activity may represent a part of mechanisms responsible for inhibition of neutrophil functions. Further studies using in vivo systems are required to elucidate inhibitory effects of pentobarbital or phenobarbital on ROS production and chemotaxis in clinical settings.