Ascorbic acid attenuates activation and cytokine production in sepsis-like monocytes

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Sammanfattning

Sepsis manifests due to the host's dysregulated immune response to infection. High-dose ascorbic acid (AA) has emerged as a potential treatment of sepsis, yet little is known regarding how AA influences the immune system in sepsis, such as monocytes. The objective of this study is to investigate the effects of high-dose AA on monocyte polarization and cytokine production in vitro. Monocytes isolated from healthy donors (n = 6) were polarized in vitro for 48 h using LPS or lipoteichoic acid (LTA). Polarization was confirmed by surface marker expression using flow cytometry. In parallel, monocytes from septic patients (n = 3) were analyzed for polarization markers as a comparison with the in vitro polarization. The effect of AA on monocyte polarization was then evaluated. Finally, monocytes were analyzed for cytokine production by intracellular staining. Both LPS and LTA induced polarization in healthy monocytes in vitro, with increased expression of both pro (M1) (CD40 and PDL1, p < 0.05) and anti-inflammatory (M2) (CD16 and CD163, p < 0.05) polarization markers. This pattern resembled that of monocytes from septic patients. Treatment with AA significantly inhibited surface expression of CD16 and CD163 (p < 0.05) in a dose-dependent manner. Finally, AA attenuated LPS- or LTA-induced cytokine production of IL-1ß, IL-6, IL-8, and TNF. In conclusion, AA attenuates proinflammatory cytokine production and diminishes up-regulation of CD16 and CD163, but not of CD40 and PDL-1 in LPS- or LTA-polarized monocytes. This study provides important insight into the effects of high-dose AA on monocytes and potential implications in sepsis.

Originalspråkengelska
TidskriftJournal of Leukocyte Biology
DOI
StatusE-pub ahead of print - 2022

Ämnesklassifikation (UKÄ)

  • Immunologi inom det medicinska området

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