Valproic acid reduces the ability of neutrophils to fight infection in epileptic patients

Valproic acid (VPA) is well established as a first-line and widely used antiepileptic agent. It is well tolerated in most patients and the main issues of concern of VPA are hematological toxicity, tertogenicity and idiosyncratic hepatotoxicity. Recently, researches have showed that VPA monotherapy could cause immunological function disorder, characterized that VPA monotherapy induced imbalance of oxidative/antioxidative status. Measures of oxidative stress were elevated while the antioxidative agent like Reduced glutathione (GSH) was degraded. Besides, antioxidants vitamin C and vitamin E can protect hepatocyte from VPA toxicity. In addition, in a eukaryon, social amoeba dictyostelium discoideum, VPA inhibit the chemotactic cell movement and endocytosis/exocytosis by attenuating its phospholipid signaling. Neutrophil is an important composition of innate immunity, it works mainly through phagocytosis and oxidization. The phagocytosis and oxidization activity are the basic and primitive function of neutrophils which are mimic to that of a eukaryon. Herein, we hypothesize that VPA, may have unexpected effects on the endocytic and oxidative function of neutrophil. The potential unfavorable subsequent events in the individuals with VPA treatment would be in the increased episodes of infection. Any agent to boost neutrophlic endocytic and antioxidative function may be helpful to the epileptic patients.