Abstract

Propofol and Immune Modulation: Unveiling Its Role in Endotoxin Tolerance and microRNA Regulation

Author(s): Ya-Ying Chang, Cheng-Wei Lu

Propofol, an anesthetic widely used in clinical practice for its sedative, hypnotic, and analgesic properties, has garnered attention not only for its ability to induce and maintain anesthesia but also for its potential immunomodulatory effects. Beyond its role in anesthesiology, propofol has emerged as a promising agent in influencing the immune system and modulating inflammatory responses. Recent studies have indicated that propofol’s impact on immune function may extend to regulating microRNA (miRNA) expression, specifically microRNA-let-7e (let-7e), which is known for its role in immune regulation and homeostasis. MicroRNAs are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level by binding to complementary sequences on target mRNAs. This regulatory function allows miRNAs to modulate various biological processes, including cell proliferation, differentiation, and immune response. Among the numerous miRNAs, let-7e stands out due to its involvement in controlling key immune pathways and maintaining balance within the immune system. By targeting inflammatory mediators and signaling molecules, let-7e helps modulate the immune response to prevent excessive activation and chronic inflammation. The concept of endotoxin tolerance, which refers to the phenomenon where repeated exposure to low doses of Lipopolysaccharide (LPS) leads to a reduced immune response upon subsequent exposure, is a critical mechanism that prevents harmful overactivation of the immune system. However, endotoxin tolerance can also have negative implications, such as increased susceptibility to secondary infections and impaired immune responses in conditions like sepsis. Understanding how anesthetic agents like propofol can influence this process is essential for optimizing patient care, especially in surgical and critical care settings. Recent research has highlighted that propofol may play a significant role in promoting endotoxin tolerance by influencing the expression of specific miRNAs, including let-7e. Through its effect on immune cell function, propofol may help modulate inflammation and reduce the severity of systemic immune responses. This modulation of immune activity can contribute to better outcomes in patients experiencing surgical procedures, trauma, or critical illnesses where excessive inflammation poses a risk of complications. This review seeks to delve into the current understanding of propofol’s immunomodulatory properties, with a particular focus on its potential role in upregulating let-7e. The mechanisms through which propofol influences miRNA expression, the implications of let-7e upregulation in immune tolerance, and the clinical relevance of these findings will be examined. By exploring the intersection of propofol, miRNA regulation, and immune modulation, we aim to provide a comprehensive overview of how this anesthetic can be leveraged in clinical practice to optimize patient outcomes, especially in cases involving systemic inflammation and immune response dysregulation. Understanding the interplay between anesthetic agents and immune regulation not only enriches our knowledge of anesthetic pharmacology but also opens up possibilities for the development of targeted therapeutic strategies. The potential for propofol to enhance endotoxin tolerance through the upregulation of let-7e highlights a novel approach to managing inflammation and immune responses during surgeries, critical care, and other clinical scenarios where immune modulation is crucial for patient recovery and long-term health.