Sevoflurane suppresses microglial M2 polarization

Area of Science:

• Neuroscience
• Immunology
• Anesthesiology

Background:

• Microglia, the immune cells of the central nervous system, exhibit M1 (classical) and M2 (alternative) activation states.
• M2 microglia possess neuroprotective properties, secreting factors like arginase 1 (Arg1), chitinase 3-like 3 (Chi3l3, Ym1), and IL-10.
• Sevoflurane, a common anesthetic, is known to promote M1 microglial activation, but its effect on M2 polarization is unclear.

Purpose of the Study:

• To investigate the impact of sevoflurane on interleukin-4 (IL-4)-induced M2 microglial activation.
• To elucidate the underlying molecular mechanisms by which sevoflurane affects M2 polarization.

Main Methods:

• Primary microglia were treated with IL-4 and/or sevoflurane.
• M2 marker gene and protein expression (Arg1, Ym1, IL-10) were assessed.
• Microglial M2 polarization induced by human umbilical cord mesenchymal stromal cell (HUC-MSC) supernatant was evaluated.
• Expression of Suppressors of Cytokine Signaling (SOCS1 and SOCS3) and STAT6 phosphorylation were analyzed.

Main Results:

• Sevoflurane significantly attenuated IL-4-induced expression of M2 markers (Arg1, Ym1, IL-10) in primary microglia.
• Sevoflurane abolished M2 polarization induced by HUC-MSC supernatant.
• Sevoflurane inhibited IL-4-induced SOCS1 expression and reversed IL-4-mediated suppression of SOCS3 expression.
• Sevoflurane suppressed STAT6 phosphorylation in primary microglia.

Conclusions:

• Sevoflurane inhibits M2 microglial polarization, counteracting IL-4-driven M2 activation.
• The anesthetic affects M2 polarization through modulation of SOCS1/SOCS3 expression and STAT6 signaling.
• These findings reveal a novel mechanism by which sevoflurane impacts microglial function, with potential implications for neuroinflammation and anesthetic-induced neurotoxicity.