Anesthetics isoflurane and sevoflurane attenuate flagellin-mediated inflammation in the lung

Yuki, Koichi; Mitsui, Yusuke; Shibamura‐Fujiogi, Miho; Hou, Lifei; Odegard, Kirsten C.; Soriano, Sulpicio G.; Priebe, Gregory P.; Koutsogiannaki, Sophia

doi:10.1016/j.bbrc.2021.04.045

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…Our results are the rst to show that iso urane exposure prior to O 3 inhibits pulmonary in ammation, whereas K/X/A exposure has an enhancing effect. These results complement other recent works that have investigated anesthesia's effects on pulmonary in ammation in response to ozone and other proin ammatory agents 5,16,19 and effects of anesthetics on the recovery of cells from BAL 20 . Although the scope of our study is limited in that we did not de ne a full time course of anesthesia's effects, our results highlight that brief, acute, anesthetic regimens can alter in ammatory responses to O 3 .…”

Section: Discussionsupporting

confidence: 88%

Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation

Wilson

Thysell

Baumann

et al. 2021

Preprint

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Anesthetics are required for procedures that deliver drugs/biologics, infectious/inflammatory agents, and toxicants directly to the lungs. However, the possible confounding effects of anesthesia on lung inflammation and injury are underreported. Here, we tested the effects of brief isoflurane (Iso) or ketamine/xylazine/atipamezole (K/X/A) anesthesia prior to ozone exposure (4 hours, 3ppm) on lung inflammatory responses in mice. Anesthesia regimens modeled those used for non-surgical intratracheal instillations, and were administered 1-2 hours or 24 hours prior to initiating ozone exposure. We found that Iso given 1-2 hours prior to ozone inhibited inflammatory responses in the lung, and this effect was absent when Iso was given 23-24 hours prior to ozone. In contrast, K/X/A given 1-2 hours prior to ozone increased lung and systemic inflammation. Our results highlight the need to comprehensively evaluate anesthesia as an experimental variable in the assessment of lung inflammation in response to ozone and other inflammatory stimuli.

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Section: Discussionsupporting

confidence: 88%

Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation

Wilson

Thysell

Baumann

et al. 2021

Preprint

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“…Our results are the first to show that isoflurane exposure prior to O 3 inhibits pulmonary inflammation, whereas K/X/A exposure has an enhancing effect. These results complement other recent works that have investigated anesthesia's effects on pulmonary inflammation in response to ozone and other pro-inflammatory agents [5,16,26] and effects of anesthetics on the recovery of cells from WLL [27]. Although the scope of our study is limited in that we did not define a full-time course of anesthesia's effects, our results highlight that brief, acute anesthetic regimens can alter inflammatory responses to O 3 .…”

Section: Discussionsupporting

confidence: 86%

Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation

Wilson

Thysell

Baumann

et al. 2022

Lung

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Purpose Anesthetics are required for procedures that deliver drugs/biologics, infectious/inflammatory agents, and toxicants directly to the lungs. However, the possible confounding effects of anesthesia on lung inflammation and injury are underreported. Here, we evaluated the effects of two commonly used anesthetic regimens on lung inflammatory responses to ozone in mice. Methods We tested the effects of brief isoflurane (Iso) or ketamine/xylazine/atipamezole (K/X/A) anesthesia prior to ozone exposure (4 h, 3 ppm) on lung inflammatory responses in mice. Anesthesia regimens modeled those used for non-surgical intratracheal instillations and were administered 1–2 h or 24 h prior to initiating ozone exposure. Results We found that Iso given 1–2 h prior to ozone inhibited inflammatory responses in the lung, and this effect was absent when Iso was given 23–24 h prior to ozone. In contrast, K/X/A given 1–2 h prior to ozone increased lung and systemic inflammation. Conclusion Our results highlight the need to comprehensively evaluate anesthesia as an experimental variable in the assessment of lung inflammation in response to ozone and other inflammatory stimuli.

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“…Human TLR7 reporter cell line HEK‐TLR7 cells containing a nuclear factor κ‐light‐chain‐enhancer of activated B cells (NFκB)‐inducible secreted embryonic alkaline phosphate (SEAP) reporter (InvivoGen; San Diego, CA, USA) were used to assess the effect of intravenous sedatives on TLR7‐mediated NFκB activation, as we previously reported 4,5,10,11 . The cells were cultured per the company's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…Human TLR7 reporter cell line HEK-TLR7 cells containing a nuclear factor κlight-chain-enhancer of activated B cells (NFκB)-inducible secreted embryonic alkaline phosphate (SEAP) reporter (InvivoGen; San Diego, CA, USA) were used to assess the effect of intravenous sedatives on TLR7-mediated NFκB activation, as we previously reported. 4,5,10,11 The cells were cultured per the company's protocol. They were stimulated with TLR7 agonist R837 (10 μg/ml) for 24 h. Sedatives (propofol, dexmedetomidine, midazolam, and fentanyl) or propofol derivative fropofol were added to corresponding wells for 24 h. The degree of NFkB activation was assessed by quantitating SEAP in the medium per the company protocol.…”

Section: Tlr Reporter Assaysmentioning

confidence: 99%

“…We previously found that volatile anesthetics isoflurane or sevoflurane did not block TLR7 activation. 10 In this study, we examined the role of common intravenous sedatives in TLR7 function and found that propofol, a common intravenous sedative used in intensive care setting and perioperative period, attenuated TLR7 activation by its direct interaction.…”

Section: Introductionmentioning

confidence: 99%

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Propofol directly binds to and inhibits TLR7

Koutsogiannaki

Maisat

et al. 2022

The FASEB Journal

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Sedatives/anesthetics are important medical tools to facilitate medical care and increase patients' comfort. Increasingly, there is recognition that sedatives/anesthetics can modulate immune functions. Toll‐like receptors (TLRs) are major pattern recognition receptors involved in the recognition of microbial components. TLR7 recognizes single‐strand RNA virus such as influenza and SARS‐CoV2 viruses and initiates interferon (IFN) responses. IFN production triggered by TLR7 stimulation is a critical anti‐viral response. For example, patients with TLR7 variants including loss‐of‐ function variants were associated with severe COVID‐19. Taken together, it is important to determine if sedatives/anesthetics mitigate TLR7 function. We have previously showed that TLR7‐mediated activation was not affected by volatile anesthetics. However, we found that propofol attenuated TLR7 activation among intravenous sedatives in the reporter assay. TLR7 agonist R837 stimulation increased TNF‐α, IL‐1β, IL‐6, IL‐10, and IFN‐β mRNA levels in bone marrow‐derived dendritic cells, while these levels were attenuated by propofol. Our murine lung slice experiments showed that propofol attenuated IFN production. R837 increased IFN‐β expression in the lungs, and propofol attenuated IFN‐β expression in an in vivo model of R837 intranasal instillation. We also found that propofol directly bound to and hindered its association of TLR7 with MyD88. Our analysis using fropofol, propofol derivative showed that the hydroxyl group in propofol was important for propofol–TLR7 interaction.

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Anesthetics isoflurane and sevoflurane attenuate flagellin-mediated inflammation in the lung

Cited by 8 publications

References 31 publications

Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation

Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation

Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation

Propofol directly binds to and inhibits TLR7

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