The Immunomodulatory Landscape of Anesthetic Agents: Mechanisms, Clinical Implications, and Therapeutic Potential.

The pharmacological actions of anesthetic agents extend far beyond neurodepression, encompassing complex immunomodulatory effects with implications for perioperative immune function, surgical outcomes, infection risk, and cancer biology. This review critically evaluates current evidence on how different anesthetic classes influence innate and adaptive immunity, examining cellular targets and signaling mechanisms. Rather than viewing anesthesia as monolithically immunosuppressive, current evidence supports a nuanced understanding in which immunological effects vary according to anesthetic agent, dose, timing, and clinical context. Volatile anesthetics (isoflurane, sevoflurane) attenuate natural killer cell cytotoxicity and neutrophil function, promote lymphocyte apoptosis with T helper 2 cell skewing, and exhibit context-dependent anti-inflammatory properties. Propofol preserves immune function by attenuating ROS-mediated cellular damage and maintaining Th1/Th2 balance. Ketamine exerts concentration-dependent immunomodulatory effects including anti-inflammatory actions on macrophages and biphasic lymphocyte modulation. We discuss clinical implications in oncological surgery, sepsis, and autoimmune disorders, emphasizing strengths and limitations of current evidence. Emerging frontiers include personalized anesthesia guided by immune phenotyping, novel targeted agents, and the gut microbiome as a modulator of anesthetic-immune interactions, though these remain promising directions rather than established practice. This review integrates mechanistic insights with clinical evidence and identifies priorities for translational research.