Effect of Propofol on the Production of Inflammatory Cytokines by Human Polarized Macrophages

• Published in: Mediators of inflammation Vol. 2019; no. 2019; pp. 1 - 13
• Main Authors: Inada, Eiichi, Takamori, Kenji, Yamane, Yui, Kage, Madoka, Nakayama, Hitoshi, Li, Xiaojia, Kochiyama, Tsukasa, Iwabuchi, Kazuhisa
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2019; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Anesthesia; Cellular signal transduction; Cytokines; Gene expression; IL-1β; Immune system; Immunology; Inflammation; Interleukin 10; Interleukin 6; Macrophages; Monocytes; Muscimol; Nuclear transport; Phenols; Polarization; Propofol; Rodents; siRNA; Surgery; Transduction; Transforming growth factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Wound healing; γ-Aminobutyric acid A receptors; Japan; United States > US
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2019/1919538

Macrophages are key immune system cells involved in inflammatory processes. Classically activated (M1) macrophages are characterized by strong antimicrobicidal properties, whereas alternatively activated (M2) macrophages are involved in wound healing. Severe inflammation can induce postoperative complications during the perioperative period. Invasive surgical procedures induce polarization to M1 macrophages and associated complications. As perioperative management, it is an important strategy to regulate polarization and functions of macrophages during inflammatory processes. Although propofol has been found to exhibit anti-inflammatory activities in monocytes and macrophages, it is unclear whether propofol regulates the functions of M1 and M2 macrophages during inflammatory processes. This study therefore investigated the effects of propofol on human macrophage polarization. During M1 polarization, propofol suppressed the production of IL-6 and IL-1β but did not affect TNF-α production. In contrast, propofol did not affect the gene expression of M2 markers, such as IL-10, TGF-β, and CD206, during M2 polarization. Propofol was similar to the GABAA agonist muscimol in inducing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and inhibiting IL-6 and IL-1β, but not TNF-α, production. Knockdown of Nrf2 using siRNA significantly reduced the effect of propofol on IL-6 and IL-1β production. These results suggest that propofol prevents inflammatory responses during polarization of human M1 macrophages by suppressing the expression of IL-6 and IL-1β through the GABAA receptor and the Nrf2-mediated signal transduction pathway.