Mechanisms of the Immunological Effects of Volatile Anesthetics: A Review

Yuki, Koichi; Eckenhoff, Roderic G.

doi:10.1213/ane.0000000000001403

Cited by 88 publications

(61 citation statements)

References 132 publications

(133 reference statements)

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“…Whereas in vitro studies have shown acute effects on microglia cytokine expression by isoflurane, no such effects were reported when examining rodent astrocyte or microglial activity at 1, 3, or 7 days after anesthesia without surgery. 1,2,55,56 To our knowledge, there is currently no experimental evidence for a persistent reduction in microglia activity after 3 to 4 days due to administration of anesthetic agents; however, a contribution of anesthesia to the reductions in TSPO observed in the present study cannot be fully excluded. Another caveat in interpreting our results is the possibility that postoperative pain may have an effect on TSPO binding.…”

Section: Annals Of Neurologymentioning

confidence: 53%

The immune response of the human brain to abdominal surgery

Forsberg

Červenka

Fagerlund

et al. 2017

Annals of Neurology

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Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and longterm impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [ 11 C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [ 11 C]PBR28 binding of 26 6 26% (mean 6 standard deviation) at 3 to 4 days postoperatively compared to baseline (p 5 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 6 39%) on the 3rd to 4th postoperative day, corresponding to changes in [ 11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [ 11 C]PBR28 binding (p 5 0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. ANN NEUROL 2017;81:572-582 A growing body of evidence suggests that surgical trauma launches a systemic inflammatory response that ultimately reaches and activates the intrinsic immune system of the brain. [1][2][3][4] Triggered by surgery-induced damage-associated molecular patterns (DAMPs), an array of proinflammatory mediators and activated blood-borne immune cells orchestrate a rapid spread of this systemic response to the central nervous system (CNS), with inflammatory markers detectable in human cerebrospinal fluid (CSF) within 12 hours. [4][5][6][7] In surgical rodent models, this periphery-to-brain pathway seems critically dependent on NF-jB and proinflammatory cytokine signaling (eg, tumor necrosis factor-a [TNF-a]) associated with a shortlasting disruption of blood-brain barrier integrity, 2,3,8 migration of peripheral macrophages into the CNS, and subsequent hippocampal neuronal dysfunction and cognitive impairment. 8 In addition to an acute and transient response, often referred to as a syndrome of sickness behavior including fatigue, anorexia, and fever, surgery-induced immune activation may be associated with prolonged impairments in learning,...

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Section: Annals Of Neurologymentioning

confidence: 53%

The immune response of the human brain to abdominal surgery

Forsberg

Červenka

Fagerlund

et al. 2017

Annals of Neurology

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“…This result suggested that their swimming defect was not due to defect in flagellin expression. It is a general consensus that anesthetic effect by volatile anesthetics is through their interaction with multiple ion channels [32]. Therefore, we predicted that swimming impairment by isoflurane would derive from its interaction with multiple ion transporters.…”

Section: Resultsmentioning

confidence: 99%

The Differential Effects of Anesthetics on Bacterial Behaviors

et al. 2017

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Volatile anesthetics have been in clinical use for a long period of time and are considered to be promiscuous by presumably interacting with several ion channels in the central nervous system to produce anesthesia. Because ion channels and their existing evolutionary analogues, ion transporters, are very important in various organisms, it is possible that volatile anesthetics may affect some bacteria. In this study, we hypothesized that volatile anesthetics could affect bacterial behaviors. We evaluated the impact of anesthetics on bacterial growth, motility (swimming and gliding) and biofilm formation of four common bacterial pathogens in vitro. We found that commonly used volatile anesthetics isoflurane and sevoflurane affected bacterial motility and biofilm formation without any effect on growth of the common bacterial pathogens studied here. Using available Escherichia coli gene deletion mutants of ion transporters and in silico molecular docking, we suggested that these altered behaviors might be at least partly via the interaction of volatile anesthetics with ion transporters.

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“…Then, Fas DD changes its conformation (2) to bind to FADD (PDB: 3EZQ) (3). Fas-FADD multimers will be more stable than monomer (4) to facilitate procaspace 8 binding (5) that leads to caspase 8 activation (6) followed by caspase-3 activation (7). Red arrows indicate predicated responses by sevoflurane exposure.…”

Section: Discussionmentioning

confidence: 99%

The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain–Fas‐associated death domain interaction

Koutsogiannaki

Hou

Babazada³

et al. 2019

The FASEB Journal

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Sepsis remains a significant health care burden, with high morbidities and mortalities. Patients with sepsis often require general anesthesia for procedures and imaging studies. Knowing that anesthetic drugs can pose immunomodulatory effects, it would be critical to understand the impact of anesthetics on sepsis pathophysiology. The volatile anesthetic sevoflurane is a common general anesthetic derived from ether as a prototype. Using a murine sepsis model induced by cecal ligation and puncture surgery, we examined the impact of sevoflurane on sepsis outcome. Different from volatile anesthetic isoflurane, sevoflurane exposure significantly improved the outcome of septic mice. This was associated with less apoptosis in the spleen. Because splenic apoptosis was largely attributed to the apoptosis of neutrophils, we examined the effect of sevoflurane on FasL‐induced neutrophil apoptosis. Sevoflurane exposure significantly attenuated apoptosis. Sevoflurane did not affect the binding of FasL to the extracellular domain of Fas receptor. Instead, in silico analysis suggested that sevoflurane would bind to the interphase between Fas death domain (DD) and Fas‐associated DD (FADD). The effect of sevoflurane on Fas DD‐FADD interaction was examined using fluorescence resonance energy transfer (FRET). Sevoflurane attenuated FRET efficiency, indicating that sevoflurane hindered the interaction between Fas DD and FADD. The predicted sevoflurane binding site is known to play a significant role in Fas DD‐FADD interaction, supporting our in vitro and in vivo apoptosis results.—Koutsogiannaki, S., Hou, L., Babazada, H., Okuno, T., Blazon‐Brown, N., Soriano, S. G., Yokomizo, T., Yuki, K. The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain‐Fas‐associated death domain interaction. FASEB J. 33, 12668–12679 (2019). http://www.fasebj.org

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Mechanisms of the Immunological Effects of Volatile Anesthetics: A Review

Cited by 88 publications

References 132 publications

The immune response of the human brain to abdominal surgery

The immune response of the human brain to abdominal surgery

The Differential Effects of Anesthetics on Bacterial Behaviors

The volatile anesthetic sevoflurane reduces neutrophil apoptosis via Fas death domain–Fas‐associated death domain interaction

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