Anesthetic modulation of immune reactions mediated by nitric oxide

Abstract

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.

A novel method for modeling facial allodynia associated with migraine in awake and freely moving rats

“…Many of the mechanisms identified to be responsible for modulating exaggerated pain states cannot be adequately studied in an anesthetized animal. Commonly used anesthetics including isoflurane, halothane, and sodium pentobarbital all affect immune cell and glial activity, beyond their well known suppression of neuronal activation (Itoh et al, 2004; Kudo et al, 2001; Martin et al, 1995; Roughan and Laming, 1998; Toda et al, 2008; Wentlandt et al, 2006; Wise-Faberowski et al, 2006). Thus these mediators cannot be accurately studied in anesthetized animals when immune and/or glial mediators are suspected as potential mediators.…”

Immune Modulation by Volatile Anesthetics

“…48,140 The suppressive effect is followed by the alteration of the NO-cyclic 3′,5′-guanosine monophosphate (NO-cGMP) system, which is a major signaling transduction pathway implicated in a wide range of physiologic functions. 140,141 Evidence showed that volatile anesthetics interacted with several upstream mediators of iNOS, including calcium, protein kinase C (PKC), and heme oxygenase-1 (HO-1). Isoflurane and desflurane at clinically relevant concentrations mediated the inhibitory effect on iNOS expression by inhibiting mobilization of cytosolic free calcium, which occurred upon macrophage activation.…”

Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before liver resection when using intermittent vascular inflow occlusion: A randomized clinical trial

“…In this respect, there are 2 important concerns: First, in the clinical setting, the presence of confounding factors (medical treatment, opioids, corticosteroids, and remote preconditioning by intermittent sequential compression devices) could influence the modulatory markers, such as apoptosis, NO expression, and interleukins; second, all anesthetics (volatile, intravenous, and local) have similar anti-inflammatory modulatory effects, because they inhibit or upregulate of NO. 32 Because in human studies it is not feasible to inhibit or activate the mechanisms involved in anesthetic modulatory protection to assess whether this mechanism is involved, the results are controversial. 18,33 All these factors should be considered in the setting of liver resection using INT.…”