Research articleSevoflurane suppresses microglial M2 polarization

•Sevoflurane abolishes M2 marker genes and proteins expression Arg1, Ym1, and IL-10.•Sevoflurane inhibits the induction of SOCS1 in primary microglia.•Sevoflurane restored the reduction of SOCS3 in primary microglia.•Sevoflurane suppresses the activation of Stat-6.•The suppression of M2 marker genes by sevoflurane is reversible.

Microglia can be polarized into the classical (M1) or alternative (M2) activation states in response to various stimuli. The M2 phenotype has its own set of receptor profiles, cytokine production, and chemokine secretion, of which arginase 1 (Arg1), chitinase 3-like 3 (Chi3l3, Ym1), and IL-10 have neuroprotective properties. Sevoflurane is one of the most commonly used volatile anesthetics in clinics. Previous studies have shown that sevoflurane promotes microglial M1 activation. However, it remains unclear whether sevoflurane regulates microglial M2 activation. In this study, we found that sevoflurane treatment abolished interleukin 4 (IL-4)-induced M2 microglial activation. Our results indicate that IL-4-mediated induction of the characteristic M2 marker genes and proteins Arg1, Ym1, and IL-10 was significantly attenuated by sevoflurane pretreatment in primary microglia. Microglial M2 polarization induced by incubation with culture supernatant from human umbilical cord mesenchymal stromal cells (HUC-MSCs) was abolished by treatment with 2% or 4% sevoflurane. Upregulation of SOCS1 and suppression of SOCS3 were shown to play a crucial role in the process of M2 microglial polarization. Our results also indicate that SOCS1 expression was induced by IL-4, but it was inhibited by pretreatment with sevoflurane. In contrast, IL-4 suppressed SOCS3 expression, which was restored by pretreatment with sevoflurane. Mechanistically, it was shown that sevoflurane suppresses STAT6 phosphorylation in primary microglia.