Related Experiment Video

Updated: Jan 4, 2026

Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device
09:36

Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device

Published on: September 24, 2020

3.1K

Volatile anesthetics isoflurane and sevoflurane directly target and attenuate Toll-like receptor 4 system

Toshiaki Okuno1, Sophia Koutsogiannaki2,3, Lifei Hou2,3

  • 1Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|November 2, 2019
PubMed

Insights

Volatile anesthetics like isoflurane and sevoflurane directly bind to and inhibit the Toll-like receptor 4 (TLR4) system. This interaction may influence patient outcomes in surgeries where TLR4 activation is relevant.

Area of Science:

  • Anesthesiology
  • Immunology
  • Molecular Biology

Background:

  • General anesthesia is essential for surgery, but the immunomodulatory effects of volatile anesthetics are not fully understood.
  • The Toll-like receptor 4 (TLR4) system plays a critical role in immune responses, particularly in perioperative settings.

Purpose of the Study:

  • To investigate the molecular mechanisms behind the immunomodulatory effects of volatile anesthetics.
  • To determine if volatile anesthetics directly interact with the TLR4 signaling pathway.

Main Methods:

  • Experiments were conducted in septic mice and in vitro cell cultures.
  • Photolabeling experiments were used to identify direct binding of anesthetics to the TLR4-myeloid differentiation-2 (MD-2) complex.
  • Expression of neutrophil markers and production of inflammatory mediators were analyzed.

Main Results:

  • Isoflurane attenuated TLR4 signaling in septic mice by reducing inflammatory mediators and neutrophil marker expression.
  • In vitro studies confirmed that isoflurane and sevoflurane directly bind to the TLR4-MD-2 complex.
  • Binding sites were near critical residues for TLR4-MD-2-LPS complex formation.
  • Intravenous anesthetics, except high-dose propofol, did not attenuate TLR4 signaling.

Conclusions:

  • Volatile anesthetics isoflurane and sevoflurane directly target and inhibit the TLR4 system.
  • Anesthetic choice may impact patient outcomes in conditions involving TLR4 activation.
Keywords:
TLR4anesthesiasepsis

More Related Videos

In Vitro Method to Control Concentrations of Halogenated Gases in Cultured Alveolar Epithelial Cells04:56

In Vitro Method to Control Concentrations of Halogenated Gases in Cultured Alveolar Epithelial Cells

Published on: October 23, 2018

7.0K
Optogenetic Activation of Afferent Pathways in Brain Slices and Modulation of Responses by Volatile Anesthetics08:16

Optogenetic Activation of Afferent Pathways in Brain Slices and Modulation of Responses by Volatile Anesthetics

Published on: July 23, 2020

2.6K

Related Concept Videos

Inhalational Anesthetics: Overview01:20

Inhalational Anesthetics: Overview

Inhalation anesthetics are drugs that induce general anesthesia upon inhalation. They work by increasing the sensitivity of GABAA receptors or inhibiting NMDA receptors, leading to a decrease in central nervous system activity. The depth of anesthesia can be rapidly adjusted by changing the concentration of the inhaled gas. Some common examples of inhalational anesthetics include volatile liquids like isoflurane, desflurane, sevoflurane and gases like xenon and nitrous oxide. Isoflurane, a...
925
Parenteral Anesthetics: Overview01:24

Parenteral Anesthetics: Overview

Intravenous anesthetics are drugs administered parenterally to induce anesthesia or sedation. Propofol is a widely used agent formulated as a 1% emulsion in soybean oil, glycerol, and egg phosphatide. It induces rapid anesthesia primarily due to its rapid distribution from the bloodstream to target tissues and is metabolized in the liver. However, it can cause significant pain on injection and hypertriglyceridemia. Fospropofol, a water-based prodrug of propofol, lacks these adverse effects.
533
Local Anesthetics: Mechanism of Action01:23

Local Anesthetics: Mechanism of Action

Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
3.0K
Local Anesthetics: Differential Sensitivity of Nerve Fibers01:24

Local Anesthetics: Differential Sensitivity of Nerve Fibers

Local anesthetics (LAs) block the sodium channels of nerve trunks, sensory nerve endings, and neuromuscular junctions. Although LAs can block all kinds of nerves, the sensitivity of nerve fibers differs according to nerve types and structures. LAs are known to block myelinated fibers faster than unmyelinated ones. Also, they block pain or sensory neurons at low concentrations without affecting the motor neurons involved in muscle contractions. This helps relieve labor pain without affecting the...
1.3K
Local Anesthetics: Clinical Application as Surface, Infiltration, and Conduction Block Anesthesia01:30

Local Anesthetics: Clinical Application as Surface, Infiltration, and Conduction Block Anesthesia

Depending on the target organ, local anesthetics (LAs) can be administered via various routes. In surface anesthesia, LAs are applied directly to the surface of the skin or mucous membranes. It is widely used for topical skin numbing before venipuncture or minor surgical procedures. Commonly used surface local anesthetics are lidocaine or benzocaine sprays or creams. Surface anesthesia occurs within 5 minutes and lasts for about 60 minutes. One of the main disadvantages of topical anesthesia is...
1.8K
General Anesthesia: Overview01:24

General Anesthesia: Overview

Anesthesia is a medical procedure that uses drugs for CNS suppression to enable painless surgeries and procedures. The selection of anesthetics is influenced by their pharmacokinetic properties, side effects, and patient characteristics. Various types of anesthesia include general, local, regional, spinal, and inhalational.
General anesthesia induces unconsciousness in the whole body, while the others target specific areas or sensations. It is administered to minimize adverse effects, maintain...
527