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Preclinical Pharmacology

Mechanisms of the Immunological Effects of Volatile Anesthetics: A Review

Yuki, Koichi MD*†; Eckenhoff, Roderic G. MD

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doi: 10.1213/ANE.0000000000001403
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Volatile anesthetics (VAs) have been popular drugs of choice to provide general anesthesia. These promiscuous, small molecules presumably interact with several receptors in the central nervous system (CNS) for anesthetic effect,1 and it is increasingly recognized that VAs also can target receptors outside the CNS, including those in our immune system. The studies of anesthetic effects on the immune system were already published about a century ago. Gaylord and Simpson2 reported that transplanted mammary carcinoma grew more rapidly under ether or chloroform anesthesia in mice, and Graham3 reported that ether significantly inhibited leukocyte phagocytosis of streptococci. Although these studies were not followed up for a long time, now there is a growing interest in a potential association between the choice of anesthetics and patients’ immunological outcomes. Our aim is to review potential VA targets on immune cells, suggest a model of VA effects on immune cells, and describe clinical implications.


Canonical VA Targets

Most canonical VA targets found in the CNS are ion channels, and some are expressed on leukocytes as well. Ions clearly play critical roles in leukocytes as in neurons. Divalent cations such as Ca2+ and Mg2+ act as secondary messengers for intracellular signaling, and monovalent cations (Na+, K+, and Cl) regulate the membrane potential and indirectly control Ca2+ influx.

GABAA Receptor

Table 1.:
Expression Profiles of GABAA Receptor Subunits in Human/Rodent Leukocytes

γ-Aminobutyric acid type A (GABAA) receptors are GABA-gated chloride channels and are considered important receptors underlying anesthesia.4–7 They are pentamers assembled from 19 subunits (α1–6, β1–3, γ1–3, δ, ε etc) with a typical stoichiometry (α)2-(β)2-γ (or δ, ε). α1–5 and β3 are sensitive to VAs.8–15 The subunit distribution in leukocytes is shown in Table 1.16–19 GABA inhibits T-cell proliferation and T cell-mediated delayed-type hypersensitivity response20,21 and attenuates monocyte chemotaxis and phagocytosis.18 GABA enhances Cl influx, producing hyperpolarization and an attenuation of Ca2+ influx. We suggest that GABA acts as a negative regulator in monocytes or lymphocytes via GABAA receptors, an action that should be further potentiated by VAs.

Glycine Receptors

Table 2.:
Expression Profiles of Glycine Receptor Subunits in Rodent Leukocytes

Glycine receptor (GlyR) is a pentameric glycine-gated chloride channel, assembled from α-subunits (α1–4) and/or β-subunit.22,23 Like GABAAR, receptors containing α1 and α2 are potentiated by VAs.24,25 GlyRs are expressed in macrophages and neutrophils (Table 2).26 Glycine enhances Cl influx, hyperpolarizes and attenuates Ca2+ influx, and blunts superoxide production in stimulated neutrophils.27 Glycine attenuates the activation of lipopolysaccharide (LPS)-treated monocytes28 and alveolar macrophages.29 We suggest that glycine works as a negative regulator via GlyRs in neutrophils and monocytes/macrophages, an effect that should be potentiated by VAs.

Nicotinic Acetylcholine Receptors

Table 3.:
Expression Profiles of nAChRs in Rodent Leukocytes

Nicotinic acetylcholine receptors (nAChRs) are pentameric nonselective cation channels, assembled from 16 subunits (α1–7, α9–10, β2–4, γ, δ, and ε).30 The α4β2 receptor is expressed in macrophages, and its activation enhances macrophage phagocytosis.31,32 α4β2 is also expressed in immature B cells.33 The α7 homomer is expressed in alveolar macrophages and contributes to the reduction of proinflammatory cytokines upon its activation.30,34 α4β2 is inhibited by VAs, whereas α7 is insensitive.35–38 We suggest that acetylcholine is a positive regulator of macrophage function via α4β2, which VAs can attenuate. Although a majority of B cells mediate acquired immunity with a half-life on the order of weeks,39 some B cells have innate functions,40 which VAs may influence in unclear ways (Table 3).

Serotonin Receptors

Table 4.:
Expression Profiles of 5-HT Subtypes in Human and Rodent Leukocytes

The expression profile of serotonin receptors (5-HTs) in leukocytes is shown in Table 4.41,42 Serotonin enhances macrophage phagocytosis via 5-HT1A.43 5-HT1B, 5-HT1E, and 5-HT2B induce chemotaxis of immature dendritic cells,41 whereas 5-HT4 and 5-HT7 in mature dendritic cells reduce Th1 cytokine release. Serotonin also induces migration of mast cells and eosinophils and is involved in T-cell proliferation. In general, VAs attenuate 5-HT1A, 5-HT2B, and 5-HT7 activity.44 We suggest that serotonin functions as a positive regulator via 5-HTs in macrophages, dendritic cells, eosinophils, and T cells, an effect that may be attenuated by VAs.

N-Methyl-d-Aspartate Receptor

Table 5.:
Expression Profiles of N-Methyl-d-Aspartate Receptor Subunits in Human and Rodent Leukocytes

The N-methyl-d-aspartate (NMDA) receptor is an ionotropic glutamate receptor.45 This ligand-gated nonselective cation channel is considered to be a prime VA target, assembled from NR1, NR2 (NR2A-D), and NR3.46–48 NR1 and NR2B subunits are present in resting T cells, and NR1, NR2A, NR2B, and NR2D subunits are detected in phytohemagglutinin-activated T cells.47 The inhibition of NMDA receptors impairs T-cell proliferation.49 Zymosan-activated neutrophils express NR1/NR2B, which may be involved in reactive oxygen species production. VAs inhibit NR1/NR2A and NR1/NR2B.50,51 We suggest that NMDA receptors act as positive regulators in neutrophils and T cells, an effect that VAs may attenuate (Table 5).

Potassium Channel

Potassium channels are classified into at least 4 types; calcium-activated channels (Kca), voltage-gated channels (Kv), inward rectifying channels, and tandem pore domain channels (K2P). Kv and Kca channels are major potassium channels in leukocytes. The K2P channel is also expressed in leukocytes and has been increasingly recognized as a prime VA target.52 Because VAs affect inward rectifying channels minimally,53 we will not review them here.

Kca 3.1 and Kv1.3 are major potassium channels in T and natural killer (NK) cells54–56 and are also expressed in macrophages54 and neutrophils.57 VAs inhibit Kca3.1 but potentiate Kv3.1.58,59 Among the members of K2P channel, TASK-1, -2, and -3 are expressed in T cells,59,60 and TASK-2 is expressed in NK cells.55 Activation of K2P channel hyperpolarizes the cell and reduces activation. TASK-1, -2, and -3 are potentiated by VAs.61–65 The role of potassium channels has been studied most in T cells.59 Kca3.1, Kv1.3, and K2P channels counterbalance calcium-induced depolarization of the plasma membrane to allow more Ca2+ influx into T cells. The divided contribution of a K+ outward current in human CD3+ T cells is 40% through Kv1.3, 20% through Kca1.3, and 40% through K2P channels. VAs may potentiate the K+ efflux via their interaction with Kv1.3 and K2P channels and reduce it via Kca3.1. Overall, the plasma membrane potential of neutrophils, macrophages, and T cells is regulated by potassium channels, an effect that VAs can alter in a heterogeneous manner.

Sodium Channel

Among voltage-gated sodium channels (Nav), Nav1.2, Nav1.4, Nav1.5, Nav1.6, and Nav1.8 are sensitive to VAs.66 Nav1.5 is expressed in the late endosome of macrophage and regulates phagocytosis.67,68 This channel is also essential for the positive selection of CD4+ T cells.69 We suggest that VAs attenuate the activation of macrophage phagocytic function via Nav1.5, but positive selection is a long-term process, which might not be influenced by short exposure to VAs.

Noncanonical Target: β2 Integrin

Previously, we demonstrated that 2% isoflurane exposure for 2 and 4 hours reduced neutrophil migration by 85% to 90% in the reverse Arthus reaction model, a well-known skin inflammation model.70 Although many molecules are involved in neutrophil recruitment, the β2 integrins are essential, because their depletion completely abolished neutrophil migration. In addition, the ex vivo study by Möbert et al,71 showing that neutrophils exposed to isoflurane or sevoflurane had reduced adhesion to human umbilical vein endothelial cells, provided a rationale for a closer study of the β2 integrins.

Integrins are adhesion molecules consisting of α- and β-subunits (18 α- and 8 β-subunits) (Figure 1A).72 β2 integrins are expressed only in leukocytes, and thus are also called “leukocyte integrins” and include αLβ2 (a.k.a., LFA-1), αMβ2 (a.k.a., Mac-1), αXβ2, and αDβ2. LFA-1 is expressed in all leukocytes and facilitates leukocyte arrest, as well as immunological synapse formation on NK, T, and B cells. Mac-1 is largely expressed on neutrophils, monocytes, and macrophages and underlies intravascular “crawling” on the endothelium and complement-mediated phagocytosis. The in vivo role of αXβ2 and αDβ2 is still unclear. The molecules responsible for leukocyte recruitment in different tissues and pathophysiologic states are likely different,73 nevertheless, a requirement for LFA-1 and Mac-1 well described and important in leukocyte adhesion deficiency.

Figure 1.:
The conformational changes of β2 integrins with inside-out signal. A, With activation, the conformation of β2 integrins changes from a bent conformation (left) to an extended conformation (right). β2 integrins can bind to their ligands only when they are fully activated. α indicates α-subunit; β, β-subunit. The blue arrow shows the downward displacement of C terminus in the α I domain. B, The scheme of inside-out signal, β2 activation, and subsequent ligand binding.
Figure 2.:
The concerted effects of volatile anesthetics on target receptors in neutrophils. Signals via cytokine and/or chemokine receptors increase intracellular calcium concentration and activate β2 integrins. Intracellular calcium influx can be enhanced by the N-methyl-d-aspartate (NMDA) receptor, voltage-gated potassium channel (Kv), and calcium-activated potassium channel (Kca) and attenuated by the glycine receptor (GlyR). The effect of volatile anesthetics on these targets is summarized. The subtypes of Kv and Kca channels are not known and need to be studied, as well as the effect of volatile anesthetics.

The major ligand-binding domain (called the α I domain) for β2 integrins is located in the α-subunit.72,74 Integrins undergo dynamic conformational changes, which include the α I domain upon activation (Figure 1A). With extracellular activation of leukocytes, LFA-1 and Mac-1 become active (inside-out signal) (Figure 1B) and then bind to their ligands. This involves the pull-down and unwinding of the α7 helix of the α I domain (“extended conformation”) and conformational rearrangements of the ligand-binding site at the α I domain from a low- to a high-affinity configuration, only the latter of which can tightly bind to ligands (Figure 2). The LFA-1 antagonist lovastatin works by binding to the pocket underneath this α7 helix, impairing ligand binding. Isoflurane and sevoflurane also bind to this “lovastatin site”75–77 and inhibit LFA-1. Mac-1, which is structurally similar to LFA-1, was inhibited by isoflurane but not by sevoflurane.75 We suggest that VAs modulate neutrophil and macrophage recruitment via LFA-1 and/or Mac-1, and phagocytosis via Mac-1, and T cell and B cell recruitment via LFA-1.


Describing the effect of VAs on individual targets in leukocytes does not provide a complete understanding of how VAs affect their function. Bridging the gap between molecular and cellular effects requires an appreciation of how these proteins are integrated within the cell. Although additional VA targets in leukocytes may exist, it is nonetheless important to construct a model of how VAs affect the regulation of leukocyte function. VA target receptors in leukocytes are summarized in Table 6, and here, we review neutrophils, macrophages, and NK cells as examples.

Table 6.:
Possible VA Target Receptors on Leukocytes


Circulating neutrophils are rapidly primed to extravasate and migrate toward a site of inflammation/infection. During surgery, the time frame of neutrophil recruitment overlaps with the exposure to VAs, making neutrophils prime targets for VA-mediated immunological effects.

Neutrophil recruitment consists of rolling, adhesion, and transmigration. These events are triggered by chemoattractants and inflammatory mediators, which activate neutrophils (inside-out signal) (Figure 1B). The many molecules responsible for neutrophil recruitment have been reviewed elsewhere in detail.73,78 In general, activated neutrophils attach and roll along the endothelium via the selectins (E- and P-selectins on the endothelium and L-selectin on neutrophils). Later, firm adhesion on the endothelium is mediated by the β2 integrins, principally LFA-1 and Mac-1.79 Finally, neutrophils transmigrate through the endothelium to the site of inflammation/infection to mediate a complex array of antibacterial effects, including phagocytosis, generation of toxic reactive oxygen species, secretion of proteases and antimicrobial peptides, neutrophil extracellular traps, as well as mediators that attract additional neutrophils, and macrophages and lymphocytes. The antibacterial products of neutrophils are also responsible for inflammation and tissue destruction encountered during recovery from bacterial infection, sepsis, and ischemia/reperfusion injury.80,81 Phagocytosis of foreign particles/organisms is mediated by complement receptors (such as Mac-1) and Fcγ receptors.82–84

VAs target LFA-1, Mac-1, GlyR, Kv, and Kca channels and NMDA receptors in neutrophils (Table 6). Intracellular calcium serves as a secondary messenger to activate neutrophils, and its concentration is a sensitive indicator of activation.85,86 Intracellular calcium regulates and directly activates β2 integrins (inside-out signal).85 NMDA receptors may enhance intracellular calcium signaling. Potassium efflux via Kv and Kca channels may counterbalance Ca2+ influx, sustaining the resting membrane potential and further enhancing Ca2+ influx as in T cells. The role of Cl efflux is more clearly understood. Resting neutrophils have an atypically high, intracellular Cl concentration (80–90 mM).87 Tumor necrosis factor (TNF)-α stimulation causes Cl efflux in neutrophils. The Cl inhibitor ethacrynic acid blocks continuous Cl efflux, cell spreading, and superoxide production in TNF-α-stimulated neutrophils. Furthermore, resuspension of neutrophils in Cl-free medium results in massive Cl efflux, Ca2+ influx, enhanced adhesion, and superoxide production, demonstrating that Cl efflux and Ca2+ influx themselves lead to neutrophil and β2 integrin activation.88 GlyR, however, enhances Cl influx. Cl influx hyperpolarizes the cell membrane, which presumably reduces Ca2+ influx27 and the likelihood of neutrophil activation. Figure 2 summarizes the potential effects of VAs on neutrophils.


Macrophages are considered a “professional” phagocyte. Monocytes circulate through bone marrow and extravasate to tissues and differentiate into macrophages.89 Macrophages can be divided into different subsets based on their molecular expression profiles; “classically” activated macrophages are M1 macrophages and “alternatively” activated macrophages are M2 macrophages. M1 macrophages can be induced by interferon-γ and LPS stimulation in vitro, and they mediate host defense with high microbicidal activity, whereas M2 macrophages are induced by interleukin (IL)-4 and IL-13 in vitro and mediate antiinflammatory effect and phagocytosis and help tissue healing.90

Figure 3.:
The targets of volatile anesthetics in macrophages and their biological roles. Volatile anesthetic target receptors and ion channels in macrophages are shown. ER indicates endoplasmic reticulum; GABA, γ-aminobutyric acid; IL, interleukin; TNF, tumor necrosis factor.

The GlyR, GABAA-receptor, nAChR, 5-HT1A, LFA-1, Mac-1, Kca3.1, Kv1.3, and Nav1.5 are all VA targets on macrophages/monocytes. GlyR allows Cl influx and hyperpolarizes the membrane, inhibiting a rise in intracellular calcium, superoxide, and TNF-α secretion.26,29 Activation of the GABAAR reduced IL-6 and IL-12 production in LPS-stimulated macrophages,91 whereas stimulation of nAChR α4β2 with agonists attenuated intracellular calcium and NF-kB activation32 but enhanced phagocytosis.31 Both Kca3.1 and Kv1.3 regulate calcium influx,92 and their blockade reduced chemotactic migration.93,94 Nav1.5 is expressed on the late endosome and contributes to the generation of prolonged and localized calcium oscillations during phagosome formation.67 The activation of 5-HT1A enhances phagocytosis.95 The interactions among these ion channels and receptors have not been much studied in macrophages, but the final effect is unlikely to be a simple sum of the individual actions. We summarized the interactions of VAs on target receptors in macrophages in Figure 3.

NK Cells

Figure 4.:
The targets of volatile anesthetics on natural killer cells and their biological roles. Once natural killer (NK) cells bind to target cells (conjugation), they polarize and degranulate granzyme, perforin, and FAS ligand to produce target cell cytotoxicity. LFA-1 is critical for adhesion to target cells (conjugation), and TASK-2 is also involved in LFA-1-dependent adhesion, as well as degranulation. Kca3.1 and Kv1.3 channels are involved in degranulation.

NK cells are a phenotypically distinct population of cytotoxic lymphocytes that are critical for innate immunity. They express a number of activating and inhibitory receptors and can respond to a variety of target cells, including viral infected cells and tumor cells, and lyse them without prior immunization.96 The decision to lyse target cells is determined by a delicately balanced input to NK cells from these activating and inhibitory receptors. LFA-1 is one of the critical activating receptors on NK cells involved in binding to target cells (conjugation) and providing signals to lyse target cells.97 The binding of LFA-1 to intercellular adhesion molecule-1 reorganizes cytoskeletal structures within NK cells and causes degranulation and cell lysis.98 An elevation of intracellular calcium is a requisite step for this killing process.99 Potassium channels counterbalance the depolarization induced by a rise of intracellular calcium level55 and have been shown to be involved in the adhesion of NK cells to target cells, as well as cytotoxicity.100 LFA-1, Kca3.1, Kv3.1, and TASK-2 are all receptors that VAs can target in NK cells. Among them, LFA-1 and TASK-2 are both involved in LFA-1-dependent adhesion to target cells.55 A TASK-2 antagonist attenuated calcium influx, preventing depolarization and the release of lytic granules. Similarly, blockade of Kv1.3 reduced calcium influx,55 and thereby NK cell degranulation.56 However, Kca1.3 blockade enhanced the NK degranulation but did not affect attachment to target cells.56 The summary is in Figure 4, demonstrating the various potential effects of VAs on NK cell functions.

Clinical Considerations in the Perioperative Periods

Our body has multilayered defense mechanisms against the outside world. Skin and mucosa are the most exposed tissues and act as the first line of defense against various organisms. Surgical procedures usually disrupt these barriers and introduce various organisms to otherwise sterile sites. Also tissue injury itself triggers acute inflammation (“sterile inflammation”). Adequate recruitment of circulating leukocytes to the site is critical for cleaning the site and promoting wound healing. In addition, some surgical procedures involve more extreme forms of pathophysiology such as ischemia-reperfusion. During tumor resection, immune cells may have to keep fighting to eradicate disseminated tumor cells. The role of VAs in these circumstances is briefly reviewed.

Ischemia-Reperfusion Injury

Ischemia-reperfusion is a common experience in many surgical procedures (eg, Pringle maneuver, unclamping of cross-clamped arteries, reestablishment of blood flow during transplantation) or after relief of vascular obstruction (eg, relieving malrotation of guts, embolectomy). This is considered an extreme example of sterile inflammation. Among immune cells, neutrophil recruitment plays a central role in the pathogenesis,101,102 and the activation of β2 integrins is critical. The benefit of VAs in ischemia-reperfusion has been shown in various organs and tissues including kidney,103 lung,104 and coronary artery/ myocardium in animal models.102,105 In a study using healthy human volunteers, sevoflurane (even at 0.5%–1%) protected forearm ischemia-reperfusion injury via an attenuation of neutrophil activation.106 The benefit of VAs in clinical settings is also reported in cardiac surgery.107 These results, while sparse, support a role for VAs in mitigating sterile inflammation.

Tumor Immunology

Although surgical resection is considered a gold standard of solid tumor management, recurrence or metastasis remains the major cause of death.108 The postulated, underlying mechanisms include the mechanical dissemination of tumor cells intraoperatively and promotion of local and distal metastasis by attenuation of cell-mediated immunity.109 A growing literature suggests that the type of anesthesia/anesthetics is associated with the frequency of tumor recurrence or metastasis. In general, less general anesthesia is associated with less recurrence or metastasis, or better outcomes110–114 and these studies were previously reviewed in detail.115 A recent retrospective study showed that patients receiving VAs for their surgery were associated with a hazard ratio of 1.59 for death on the univariate analysis and 1.46 after the multivariate analysis compared with the patients receiving total IV anesthesia, suggesting that VAs may not be beneficial in tumor surgery.116 Perioperative NK cell suppression correlates with higher recurrence and mortality in patients.117,118 As stated earlier, VAs should impair NK conjugation and degranulation via inhibiting LFA-1 and TASK-2. However, VAs could enhance degranulation through their interaction with Kca3.1 and Kv1.3. Given that conjugation precedes degranulation, VAs presumably impair NK cell cytotoxicity, but further study is warranted to confirm these provocative findings.


Perioperative infection is one of the most common perioperative complications. Von Dossow et al119 examined alcoholic patients who underwent resection of upper gastrointestinal tract under general anesthesia either with propofol or isoflurane. Postoperative infection rate was lower in the propofol group (23%) than in the isoflurane group (67%). Chang et al120 studied the incidence of surgical site infection in patients who underwent orthopedic procedures under regional anesthesia (spinal or epidural anesthesia) or general anesthesia and found that the general anesthesia arm had a higher incidence of surgical site infection (2.8%) over the regional anesthesia arm (1.2%). Although the detailed information of the general anesthetics was not reported, VAs would presumably be the major anesthetics in their general anesthesia group. Leukocyte recruitment and subsequent killing of microbes are required to minimize perioperative infection. Several animal studies have demonstrated that VAs modify leukocyte adhesion and recruitment.71,105,121–126 The number of recruited leukocytes to tissues is determined by a balance between proinflammatory signals and antiinflammatory signals (resolution). The intravital microscopic experiment of mesenteric circulation in LPS-induced inflammation showed that isoflurane exposure increased the speed of leukocyte rolling,122 which could lead to impaired adhesion and transmigration. Our study using the reverse Arthus reaction model in mice showed impaired neutrophil migration by isoflurane.70 Although the proinflammatory mediators in these models recruit leukocytes, resolution agonists such as lipoxins and resolvins limit further recruitment,127 but the effect of VAs on resolution agonists was not reported.126 The role of VAs on bacterial killing has also been studied. Ex vivo studies in patients (ASA physical status I–III) undergoing abdominal surgery showed a reduction of granulocyte phagocytosis and oxidative burst after 1 hour of sevoflurane or xenon anesthesia.128 Also in an ex vivo study using patients who underwent orthopedic procedures, a time-dependent reduction of phagocytic function and bacterial killing was reported to occur under isoflurane anesthesia.129

Postoperative Cognitive Dysfunction

Change in personality or cognitive ability after surgery is considered a significant form of morbidity. The causes are likely multifactorial, including a host of preoperative comorbidities, and inflammation, stress, and infection resulting from surgery and anesthesia. TNF-α and its downstream mediator IL-1β play a role in cognitive dysfunction in animal models.130,131 Cognitive dysfunction produced by TNF-α/IL-1β in mice occurred via the α5GABAA receptor. Activation of this receptor appears to impair memory and IL-1β-induced prolonged α5GABAA receptor expression.132 Furthermore, isoflurane caused a persistent tonic current via α5GABAA receptor.133

Microglia, which are analogous to macrophages in the brain, secrete a variety of proinflammatory mediators, so attenuating this neuroinflammation may help to reduce postoperative memory and perhaps cognitive deficits. In a study of isolated microglia, isoflurane had little effect on LPS-stimulated proinflammatory cytokine release, while sevoflurane enhanced it.134 In patients undergoing esophageal tumor resection under sevoflurane anesthesia or propofol anesthesia, cognitive decline was more apparent in the sevoflurane anesthesia group and was associated with higher plasma IL-6 and TNF-α concentrations. Finally, in a rare randomized controlled study of older patients getting spinal surgery, and with mild preexisting cognitive deficits, those receiving sevoflurane anesthesia declined more rapidly compared with regional or propofol.135 These studies suggest that VAs may contribute to postoperative cognitive decline, but it is becoming clear that many other factors are involved.


Although clinical studies on the association between VAs and immunological issues are limited, this review highlights a molecular biological basis of VA-induced immunomodulation and hopefully facilitates clinical studies on perioperative immunological outcomes in the future.


Name: Koichi Yuki, MD.

Contribution: This author helped design and prepare the manuscript.

Name: Roderic G. Eckenhoff, MD.

Contribution: This author helped design and prepare the manuscript.

This manuscript was handled by: Markus W. Hollmann, MD, PhD.


1. Eckenhoff RGPromiscuous ligands and attractive cavities: how do the inhaled anesthetics work?Mol Interv2001125868
2. Gaylord H, Simpson BTThe effect of certain anesthetics and loss of blood upon the growth of transplanted mouse cancer.J Cancer Res1916137982
3. Graham EThe influence of ether and ether anesthesia on bacteriolysis, agglutination, and phagocytosis.J Infect Dis1911814775
4. Olsen RW, Tobin AJMolecular biology of GABAA receptors.FASEB J19904146980
5. Goetz T, Arslan A, Wisden W, Wulff PGABA(A) receptors: structure and function in the basal ganglia.Prog Brain Res20071602141
6. Garcia PS, Kolesky SE, Jenkins AGeneral anesthetic actions on GABA(A) receptors.Curr Neuropharmacol2010829
7. Verkman AS, Galietta LJChloride channels as drug targets.Nat Rev Drug Discov2009815371
8. Nishikawa K, Harrison NLThe actions of sevoflurane and desflurane on the gamma-aminobutyric acid receptor type A: effects of TM2 mutations in the alpha and beta subunits.Anesthesiology20039967884
9. Sonner JM, Cascio M, Xing Y, Fanselow MS, Kralic JE, Morrow AL, Korpi ER, Hardy S, Sloat B, Eger EI II, Homanics GEAlpha 1 subunit-containing GABA type A receptors in forebrain contribute to the effect of inhaled anesthetics on conditioned fear.Mol Pharmacol200568618
10. Werner DF, Swihart A, Rau V, Jia F, Borghese CM, McCracken ML, Iyer S, Fanselow MS, Oh I, Sonner JM, Eger EI II, Harrison NL, Harris RA, Homanics GEInhaled anesthetic responses of recombinant receptors and knockin mice harboring α2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane.J Pharmacol Exp Ther201133613444
11. Schofield CM, Harrison NLTransmembrane residues define the action of isoflurane at the GABAA receptor alpha-3 subunit.Brain Res20051032305
12. Jia F, Yue M, Chandra D, Homanics GE, Goldstein PA, Harrison NLIsoflurane is a potent modulator of extrasynaptic GABA(A) receptors in the thalamus.J Pharmacol Exp Ther2008324112735
13. Caraiscos VB, Newell JG, You-Ten KE, Elliott EM, Rosahl TW, Wafford KA, MacDonald JF, Orser BASelective enhancement of tonic GABAergic inhibition in murine hippocampal neurons by low concentrations of the volatile anesthetic isoflurane.J Neurosci20042484548
14. Lecker I, Yin Y, Wang DS, Orser BAPotentiation of GABAA receptor activity by volatile anaesthetics is reduced by α5GABAA receptor-preferring inverse agonists.Br J Anaesth2013110suppl 1i7381
15. Rau V, Oh I, Liao M, Bodarky C, Fanselow MS, Homanics GE, Sonner JM, Eger EI IIGamma-aminobutyric acid type A receptor β3 subunit forebrain-specific knockout mice are resistant to the amnestic effect of isoflurane.Anesth Analg20111135004
16. Alam S, Laughton DL, Walding A, Wolstenholme AJHuman peripheral blood mononuclear cells express GABAA receptor subunits.Mol Immunol200643143242
17. Dionisio L, José De Rosa M, Bouzat C, Esandi Mdel CAn intrinsic GABAergic system in human lymphocytes.Neuropharmacology2011605139
18. Wheeler DW, Thompson AJ, Corletto F, Reckless J, Loke JC, Lapaque N, Grant AJ, Mastroeni P, Grainger DJ, Padgett CL, O’Brien JA, Miller NG, Trowsdale J, Lummis SC, Menon DK, Beech JSAnaesthetic impairment of immune function is mediated via GABA(A) receptors.PLoS One20116e17152
19. Jin Z, Mendu SK, Birnir BGABA is an effective immunomodulatory molecule.Amino Acids2013458794
20. Tian J, Chau C, Hales TG, Kaufman DLGABA(A) receptors mediate inhibition of T cell responses.J Neuroimmunol199996218
21. Tian J, Lu Y, Zhang H, Chau CH, Dang HN, Kaufman DLGamma-aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model.J Immunol20041735298304
22. Betz H, Laube BGlycine receptors: recent insights into their structural organization and functional diversity.J Neurochem200697160010
23. Lynch JWMolecular structure and function of the glycine receptor chloride channel.Physiol Rev200484105195
24. Downie DL, Hall AC, Lieb WR, Franks NPEffects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes.Br J Pharmacol1996118493502
25. Harrison NL, Kugler JL, Jones MV, Greenblatt EP, Pritchett DBPositive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.Mol Pharmacol19934462832
26. Froh M, Thurman RG, Wheeler MDMolecular evidence for a glycine-gated chloride channel in macrophages and leukocytes.Am J Physiol Gastrointest Liver Physiol2002283G85663
27. Wheeler M, Stachlewitz RF, Yamashina S, Ikejima K, Morrow AL, Thurman RGGlycine-gated chloride channels in neutrophils attenuate calcium influx and superoxide production.FASEB J20001447684
28. Spittler A, Reissner CM, Oehler R, Gornikiewicz A, Gruenberger T, Manhart N, Brodowicz T, Mittlboeck M, Boltz-Nitulescu G, Roth EImmunomodulatory effects of glycine on LPS-treated monocytes: reduced TNF-alpha production and accelerated IL-10 expression.FASEB J19991356371
29. Wheeler MD, Thurman RGProduction of superoxide and TNF-alpha from alveolar macrophages is blunted by glycine.Am J Physiol1999277L9529
30. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJNicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.Nature20034213848
31. van der Zanden EP, Snoek SA, Heinsbroek SE, Stanisor OI, Verseijden C, Boeckxstaens GE, Peppelenbosch MP, Greaves DR, Gordon S, De Jonge WJVagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2.Gastroenterology2009137102939, 1039.e1–4
32. Nemethova A, Michel K, Gomez-Pinilla PJ, Boeckxstaens GE, Schemann MNicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.PLoS One20138e79264
33. Skok MV, Grailhe R, Agenes F, Changeux JPThe role of nicotinic receptors in B-lymphocyte development and activation.Life Sci20078023346
34. Su X, Matthay MA, Malik ABRequisite role of the cholinergic alpha7 nicotinic acetylcholine receptor pathway in suppressing Gram-negative sepsis-induced acute lung inflammatory injury.J Immunol201018440110
35. Flood P, Ramirez-Latorre J, Role LAlpha 4 beta 2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha 7-type nicotinic acetylcholine receptors are unaffected.Anesthesiology19978685965
36. Violet JM, Downie DL, Nakisa RC, Lieb WR, Franks NPDifferential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics.Anesthesiology19978686674
37. Yamashita M, Mori T, Nagata K, Yeh JZ, Narahashi TIsoflurane modulation of neuronal nicotinic acetylcholine receptors expressed in human embryonic kidney cells.Anesthesiology20051027684
38. Downie DL, Vicente-Agullo F, Campos-Caro A, Bushell TJ, Lieb WR, Franks NPDeterminants of the anesthetic sensitivity of neuronal nicotinic acetylcholine receptors.J Biol Chem20022771036773
39. Fulcher DA, Basten AB cell life span: a review.Immunol Cell Biol19977544655
40. Kelly-Scumpia KM, Scumpia PO, Weinstein JS, Delano MJ, Cuenca AG, Nacionales DC, Wynn JL, Lee PY, Kumagai Y, Efron PA, Akira S, Wasserfall C, Atkinson MA, Moldawer LLB cells enhance early innate immune responses during bacterial sepsis.J Exp Med2011208167382
41. Ahern GP5-HT and the immune system.Curr Opin Pharmacol2011112933
42. Surmiak M, Kaczor M, Sanak MExpression profile of proinflammatory genes in neutrophil-enriched granulocytes stimulated with native anti-PR3 autoantibodies.J Physiol Pharmacol20126324956
43. Nakamura K, Sato T, Ohashi A, Tsurui H, Hasegawa HRole of a serotonin precursor in development of gut microvilli.Am J Pathol200817233344
44. Matsunaga F, Gao L, Huang XP, Saven JG, Roth BL, Liu RMolecular interactions between general anesthetics and the 5HT2B receptor.J Biomol Struct Dyn2015332118
45. Mayer ML, Armstrong NStructure and function of glutamate receptor ion channels.Annu Rev Physiol20046616181
46. Boldyrev AA, Kazey VI, Leinsoo TA, Mashkina AP, Tyulina OV, Johnson P, Tuneva JO, Chittur S, Carpenter DORodent lymphocytes express functionally active glutamate receptors.Biochem Biophys Res Commun20043241339
47. Miglio G, Varsaldi F, Lombardi GHuman T lymphocytes express N-methyl-D-aspartate receptors functionally active in controlling T cell activation.Biochem Biophys Res Commun2005338187583
48. Miglio G, Dianzani C, Fallarini S, Fantozzi R, Lombardi GStimulation of N-methyl-D-aspartate receptors modulates Jurkat T cell growth and adhesion to fibronectin.Biochem Biophys Res Commun20073614049
49. Bryushkova EA, Vladychenskaya EA, Stepanova MS, Boldyrev AAEffect of homocysteine on properties of neutrophils activated in vivo.Biochemistry (Mosc)20117646772
50. Hollmann MW, Liu HT, Hoenemann CW, Liu WH, Durieux MEModulation of NMDA receptor function by ketamine and magnesium. Part II: interactions with volatile anesthetics.Anesth Analg200192118291
51. Ogata J, Shiraishi M, Namba T, Smothers CT, Woodward JJ, Harris RAEffects of anesthetics on mutant N-methyl-D-aspartate receptors expressed in Xenopus oocytes.J Pharmacol Exp Ther200631843443
52. Franks NP, Honoré EThe TREK K2P channels and their role in general anaesthesia and neuroprotection.Trends Pharmacol Sci2004256018
53. Stadnicka A, Bosnjak ZJ, Kampine JP, Kwok WMModulation of cardiac inward rectifier K(+)current by halothane and isoflurane.Anesth Analg20009082433
54. Feske S, Wulff H, Skolnik EYIon channels in innate and adaptive immunity.Annu Rev Immunol201533291353
55. Schulte-Mecklenbeck A, Bittner S, Ehling P, Döring F, Wischmeyer E, Breuer J, Herrmann AM, Wiendl H, Meuth SG, Gross CCThe two-pore domain K2 P channel TASK2 drives human NK-cell proliferation and cytolytic function.Eur J Immunol201545260214
56. Koshy S, Wu D, Hu X, Tajhya RB, Huq R, Khan FS, Pennington MW, Wulff H, Yotnda P, Beeton CBlocking KCa3.1 channels increases tumor cell killing by a subpopulation of human natural killer lymphocytes.PLoS One20138e76740
57. Krause KH, Welsh MJVoltage-dependent and Ca2(+)-activated ion channels in human neutrophils.J Clin Invest1990854918
58. Lioudyno MI, Birch AM, Tanaka BS, Sokolov Y, Goldin AL, Chandy KG, Hall JE, Alkire MTShaker-related potassium channels in the central medial nucleus of the thalamus are important molecular targets for arousal suppression by volatile general anesthetics.J Neurosci2013331631022
59. Meuth SG, Bittner S, Meuth P, Simon OJ, Budde T, Wiendl HTWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions.J Biol Chem20082831455970
60. Bittner S, Bobak N, Herrmann AM, Göbel K, Meuth P, Höhn KG, Stenner MP, Budde T, Wiendl H, Meuth SGUpregulation of K2P5.1 potassium channels in multiple sclerosis.Ann Neurol2010685869
61. Liu C, Au JD, Zou HL, Cotten JF, Yost CSPotent activation of the human tandem pore domain K channel TRESK with clinical concentrations of volatile anesthetics.Anesth Analg200499171522
62. Patel AJ, Honoré E, Lesage F, Fink M, Romey G, Lazdunski MInhalational anesthetics activate two-pore-domain background K+ channels.Nat Neurosci199924226
63. Putzke C, Hanley PJ, Schlichthörl G, Preisig-Müller R, Rinné S, Anetseder M, Eckenhoff R, Berkowitz C, Vassiliou T, Wulf H, Eberhart LDifferential effects of volatile and intravenous anesthetics on the activity of human TASK-1.Am J Physiol Cell Physiol2007293C131926
64. Gray AT, Zhao BB, Kindler CH, Winegar BD, Mazurek MJ, Xu J, Chavez RA, Forsayeth JR, Yost CSVolatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5.Anesthesiology200092172230
65. Meadows HJ, Randall ADFunctional characterisation of human TASK-3, an acid-sensitive two-pore domain potassium channel.Neuropharmacology2001405519
66. OuYang W, Hemmings HC JrIsoform-selective effects of isoflurane on voltage-gated Na+ channels.Anesthesiology2007107918
67. Carrithers MD, Dib-Hajj S, Carrithers LM, Tokmoulina G, Pypaert M, Jonas EA, Waxman SGExpression of the voltage-gated sodium channel NaV1.5 in the macrophage late endosome regulates endosomal acidification.J Immunol2007178782232
68. Carrithers LM, Hulseberg P, Sandor M, Carrithers MDThe human macrophage sodium channel NaV1.5 regulates mycobacteria processing through organelle polarization and localized calcium oscillations.FEMS Immunol Med Microbiol20116331927
69. Lo WL, Donermeyer DL, Allen PMA voltage-gated sodium channel is essential for the positive selection of CD4(+) T cells.Nat Immunol2012138807
70. Carbo C, Yuki K, Demers M, Wagner DD, Shimaoka MIsoflurane inhibits neutrophil recruitment in the cutaneous Arthus reaction model.J Anesth2013272618
71. Möbert J, Zahler S, Becker BF, Conzen PFInhibition of neutrophil activation by volatile anesthetics decreases adhesion to cultured human endothelial cells.Anesthesiology199990137281
72. Shimaoka M, Takagi J, Springer TAConformational regulation of integrin structure and function.Annu Rev Biophys Biomol Struct200231485516
73. Kolaczkowska E, Kubes PNeutrophil recruitment and function in health and inflammation.Nat Rev Immunol20131315975
74. Diamond MS, Garcia-Aguilar J, Bickford JK, Corbi AL, Springer TAThe I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b/CD18) for four distinct adhesion ligands.J Cell Biol1993120103143
75. Yuki K, Astrof NS, Bracken C, Yoo R, Silkworth W, Soriano SG, Shimaoka MThe volatile anesthetic isoflurane perturbs conformational activation of integrin LFA-1 by binding to the allosteric regulatory cavity.FASEB J200822410916
76. Yuki K, Astrof NS, Bracken C, Soriano SG, Shimaoka MSevoflurane binds and allosterically blocks integrin lymphocyte function-associated antigen-1.Anesthesiology20101136009
77. Yuki K, Bu W, Xi J, Sen M, Shimaoka M, Eckenhoff RGIsoflurane binds and stabilizes a closed conformation of the leukocyte function-associated antigen-1.FASEB J201226440817
78. Wagner DD, Frenette PSThe vessel wall and its interactions.Blood2008111527181
79. Springer TATraffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm.Cell19947630114
80. Weiss SJTissue destruction by neutrophils.N Engl J Med198932036576
81. De Greef KE, Ysebaert DK, Ghielli M, Vercauteren S, Nouwen EJ, Eyskens EJ, De Broe MENeutrophils and acute ischemia-reperfusion injury.J Nephrol19981111022
82. Thelen M, Didichenko SAG-protein coupled receptor-mediated activation of PI 3-kinase in neutrophils.Ann N Y Acad Sci199783236882
83. Arnaout MA, Melamed J, Tack BF, Colten HRCharacterization of the human complement (c3b) receptor with a fluid phase C3b dimer.J Immunol1981127134854
84. Lanier LL, Arnaout MA, Schwarting R, Warner NL, Ross GDp150/95, Third member of the LFA-1/CR3 polypeptide family identified by anti-Leu M5 monoclonal antibody.Eur J Immunol1985157138
85. Schaff UY, Yamayoshi I, Tse T, Griffin D, Kibathi L, Simon SICalcium flux in neutrophils synchronizes beta2 integrin adhesive and signaling events that guide inflammatory recruitment.Ann Biomed Eng20083663246
86. Bréchard S, Tschirhart EJRegulation of superoxide production in neutrophils: role of calcium influx.J Leukoc Biol200884122337
87. Simchowitz L, De Weer PChloride movements in human neutrophils. Diffusion, exchange, and active transport.J Gen Physiol19868816794
88. Menegazzi R, Busetto S, Dri P, Cramer R, Patriarca PChloride ion efflux regulates adherence, spreading, and respiratory burst of neutrophils stimulated by tumor necrosis factor-alpha (TNF) on biologic surfaces.J Cell Biol199613551122
89. Murray PJ, Wynn TAProtective and pathogenic functions of macrophage subsets.Nat Rev Immunol20111172337
90. Vogel DY, Heijnen PD, Breur M, de Vries HE, Tool AT, Amor S, Dijkstra CDMacrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation.J Neuroinflammation20141123
91. Reyes-García MG, Hernández-Hernández F, Hernández-Téllez B, García-Tamayo FGABA (A) receptor subunits RNA expression in mice peritoneal macrophages modulate their IL-6/IL-12 production.J Neuroimmunol2007188648
92. Moreno C, Prieto P, Macías Á, Pimentel-Santillana M, de la Cruz A, Través PG, Boscá L, Valenzuela CModulation of voltage-dependent and inward rectifier potassium channels by 15-epi-lipoxin-A4 in activated murine macrophages: implications in innate immunity.J Immunol2013191613646
93. Chung I, Zelivyanskaya M, Gendelman HEMononuclear phagocyte biophysiology influences brain transendothelial and tissue migration: implication for HIV-1-associated dementia.J Neuroimmunol20021224054
94. Toyama K, Wulff H, Chandy KG, Azam P, Raman G, Saito T, Fujiwara Y, Mattson DL, Das S, Melvin JE, Pratt PF, Hatoum OA, Gutterman DD, Harder DR, Miura HThe intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans.J Clin Invest2008118302537
95. Freire-Garabal M, Núñez MJ, Balboa J, López-Delgado P, Gallego R, García-Caballero T, Fernández-Roel MD, Brenlla J, Rey-Méndez MSerotonin upregulates the activity of phagocytosis through 5-HT1A receptors.Br J Pharmacol200313945763
96. Topham NJ, Hewitt EWNatural killer cell cytotoxicity: how do they pull the trigger?Immunology2009128715
97. Thomas LM, Peterson ME, Long EOCutting edge: NK cell licensing modulates adhesion to target cells.J Immunol201319139815
98. Barber DF, Faure M, Long EOLFA-1 contributes an early signal for NK cell cytotoxicity.J Immunol200417336539
99. Schwarz EC, Qu B, Hoth MCalcium, cancer and killing: the role of calcium in killing cancer cells by cytotoxic T lymphocytes and natural killer cells.Biochim Biophys Acta20131833160311
100. Sidell N, Schlichter LC, Wright SC, Hagiwara S, Golub SHPotassium channels in human NK cells are involved in discrete stages of the killing process.J Immunol198613716508
101. Yago T, Petrich BG, Zhang N, Liu Z, Shao B, Ginsberg MH, McEver RPBlocking neutrophil integrin activation prevents ischemia-reperfusion injury.J Exp Med2015212126781
102. Kowalski C, Zahler S, Becker BF, Flaucher A, Conzen PF, Gerlach E, Peter KHalothane, isoflurane, and sevoflurane reduce postischemic adhesion of neutrophils in the coronary system.Anesthesiology19978618895
103. Lee HT, Ota-Setlik A, Fu Y, Nasr SH, Emala CWDifferential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo.Anesthesiology2004101131324
104. Liu R, Ishibe Y, Ueda MIsoflurane-sevoflurane administration before ischemia attenuates ischemia-reperfusion-induced injury in isolated rat lungs.Anesthesiology20009283340
105. Heindl B, Reichle FM, Zahler S, Conzen PF, Becker BFSevoflurane and isoflurane protect the reperfused guinea pig heart by reducing postischemic adhesion of polymorphonuclear neutrophils.Anesthesiology19999152130
106. Lucchinetti E, Ambrosio S, Aguirre J, Herrmann P, Härter L, Keel M, Meier T, Zaugg MSevoflurane inhalation at sedative concentrations provides endothelial protection against ischemia-reperfusion injury in humans.Anesthesiology20071062628
107. Conzen PF, Fischer S, Detter C, Peter KSevoflurane provides greater protection of the myocardium than propofol in patients undergoing off-pump coronary artery bypass surgery.Anesthesiology20039982633
108. Gottschalk A, Sharma S, Ford J, Durieux ME, Tiouririne MReview article: the role of the perioperative period in recurrence after cancer surgery.Anesth Analg2010110163643
109. Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma DCancer recurrence after surgery: direct and indirect effects of anesthetic agents.Int J Cancer2012130123750
110. Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DICan anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?Anesthesiology20061056604
111. Christopherson R, James KE, Tableman M, Marshall P, Johnson FELong-term survival after colon cancer surgery: a variation associated with choice of anesthesia.Anesth Analg200810732532
112. Schlagenhauff B, Ellwanger U, Breuninger H, Stroebel W, Rassner G, Garbe CPrognostic impact of the type of anaesthesia used during the excision of primary cutaneous melanoma.Melanoma Res2000101659
113. Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI, Buggy DJAnesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis.Anesthesiology20081091807
114. Lin L, Liu C, Tan H, Ouyang H, Zhang Y, Zeng WAnaesthetic technique may affect prognosis for ovarian serous adenocarcinoma: a retrospective analysis.Br J Anaesth201110681422
115. Heaney A, Buggy DJCan anaesthetic and analgesic techniques affect cancer recurrence or metastasis?Br J Anaesth2012109suppl 1i1728
116. Wigmore TJ, Mohammed K, Jhanji SLong-term survival for patients undergoing volatile versus IV anesthesia for cancer surgery: a retrospective analysis.Anesthesiology20161246979
117. Tartter PI, Steinberg B, Barron DM, Martinelli GThe prognostic significance of natural killer cytotoxicity in patients with colorectal cancer.Arch Surg198712212648
118. Fujisawa T, Yamaguchi YAutologous tumor killing activity as a prognostic factor in primary resected nonsmall cell carcinoma of the lung.Cancer19977947481
119. Von Dossow V, Baur S, Sander M, Tønnesen H, Marks C, Paschen C, Berger G, Spies CDPropofol increased the interleukin-6 to interleukin-10 ratio more than isoflurane after surgery in long-term alcoholic patients.J Int Med Res200735395405
120. Chang CC, Lin HC, Lin HW, Lin HCAnesthetic management and surgical site infections in total hip or knee replacement: a population-based study.Anesthesiology201011327984
121. McBride WT, Armstrong MA, McBride SJImmunomodulation: an important concept in modern anaesthesia.Anaesthesia19965146573
122. Hayes JK, Havaleshko DM, Plachinta RV, Rich GFIsoflurane pretreatment supports hemodynamics and leukocyte rolling velocities in rat mesentery during lipopolysaccharide-induced inflammation.Anesth Analg2004989991006
123. Reutershan J, Chang D, Hayes JK, Ley KProtective effects of isoflurane pretreatment in endotoxin-induced lung injury.Anesthesiology20061045117
124. Lee HT, Kim M, Kim N, Billings FT IV, D’Agati VD, Emala CW SrIsoflurane protects against renal ischemia and reperfusion injury and modulates leukocyte infiltration in mice.Am J Physiol Renal Physiol2007293F71322
125. Lee HT, Emala CW, Joo JD, Kim MIsoflurane improves survival and protects against renal and hepatic injury in murine septic peritonitis.Shock2007273739
126. Chiang N, Schwab JM, Fredman G, Kasuga K, Gelman S, Serhan CNAnesthetics impact the resolution of inflammation.PLoS One20083e1879
127. Serhan CN, Chiang N, Van Dyke TEResolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators.Nat Rev Immunol2008834961
128. Fahlenkamp AV, Coburn M, Rossaint R, Stoppe C, Haase HComparison of the effects of xenon and sevoflurane anaesthesia on leucocyte function in surgical patients: a randomized trial.Br J Anaesth201411227280
129. Kotani N, Hashimoto H, Sessler DI, Kikuchi A, Suzuki A, Takahashi S, Muraoka M, Matsuki AIntraoperative modulation of alveolar macrophage function during isoflurane and propofol anesthesia.Anesthesiology199889112532
130. Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze MTumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline.Proc Natl Acad Sci U S A20101072051822
131. Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze MRole of interleukin-1beta in postoperative cognitive dysfunction.Ann Neurol2010683608
132. Wang DS, Zurek AA, Lecker I, Yu J, Abramian AM, Avramescu S, Davies PA, Moss SJ, Lu WY, Orser BAMemory deficits induced by inflammation are regulated by α5-subunit-containing GABAA receptors.Cell Rep2012248896
133. Zurek AA, Yu J, Wang DS, Haffey SC, Bridgwater EM, Penna A, Lecker I, Lei G, Chang T, Salter EW, Orser BASustained increase in α5GABAA receptor function impairs memory after anesthesia.J Clin Invest2014124543741
134. Ye X, Lian Q, Eckenhoff MF, Eckenhoff RG, Pan JZDifferential general anesthetic effects on microglial cytokine expression.PLoS One20138e52887
135. Liu Y, Pan N, Ma Y, Zhang S, Guo W, Li H, Zhou J, Liu G, Gao MInhaled sevoflurane may promote progression of amnestic mild cognitive impairment: a prospective, randomized parallel-group study.Am J Med Sci201334535560
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