Anesthetic modulation of immune reactions mediated by nitric oxide

Nitric oxide (NO), when produced via inducible NO synthase (iNOS) in excess under pathological conditions (e.g., inflammation, endotoxemia, and septic shock), may lead to tissue injury and organ dysfunction. The bioavailability of NO and the activity and expression of iNOS are regulated by anesthetic agents. Volatile anesthetics mostly suppress, but in some instances may upregulate, the lipopolysaccharide-and cytokine-induced expression of iNOS in blood vessels and macrophages. Intravenous anesthetics inhibit iNOS expression in macrophages and the liver. Local anesthetics decrease the production of NO by inhibiting iNOS expression in macrophages and increase NO production in glial cells. Based on the literature reported so far, the effects of anesthetics on iNOS expression and activity under conditions of inflammation are controversial, with the observed effects depending on the experimental methods and animal species used. On the other hand, it has been shown that volatile and intravenous anesthetics consistently prevent the development of multiple organ failure elicited by endotoxemia or septic shock. Information, although still insufficient, regarding the interactions between anesthetic agents and the detrimental effects of NO formed during inflammatory processes may help us to construct advanced strategies for anesthetizing and sedating patients with inflammation and sepsis and for anesthetic preconditioning against ischemic injury.