24 March 2026 : Review article
Review of the Effects of Anesthetic Techniques and Medications on the Immune Response During the Perioperative Period
Paweł Radkowski
ABCDEFG 1,2,3, Marta Joanna Pisula ABCDEF 4, Dawid Kamil Malicki ABCDEF 5, Maciej Szewczyk ABCDEF 6*, Karolina Marczuk ABCDEF 7, Mateusz Mamala ABCDEF 8, Łukasz Grabarczyk ABCDEFG 9
DOI: 10.12659/MSM.951077
Med Sci Monit 2026; 32:e951077
Introduction
The Immune System’s Structure and Functions
Activation of Innate and Adaptive Immunity in Response to Surgical Injury
General Anesthesia as a Modulator of the Inflammatory and Immune Response in Surgical Patients
Immunomodulatory Mechanisms of Action of General Anesthesia
Methodological Considerations and Limitations
Effects of Inhalation Anesthetics on the Immune System
Controversial Findings and Interpretative Variability
Conclusions
Future Directions
References
Table 4 Differential impact of general and regional anesthesia on immune mechanisms, cytokine profiles, and clinical outcomes [12,14–17,20,22,32,38,60–62].
| Mechanism/parameter | General anesthesia | Regional anesthesia |
|---|---|---|
| Stress response | Triggers a strong surgical stress response | Reduces surgical stress response |
| Neuroendocrine modulation | Activates the HPA axis and the sympathetic nervous system | Limits activation of the HPA axis and sympathetic nervous system |
| Hormonal response | Increases cortisol and catecholamine secretion | Decreases cortisol and catecholamine secretion |
| Cytokine profile | Decreases IL-6, TNF-α, IL-1β (pro-inflammatory); increases IL-10 (anti-inflammatory) | Lowers pro-inflammatory cytokines (eg, IL-6, TNF-α); reduces systemic inflammatory response |
| Inflammatory response | Promotes immunosuppression and a weakened inflammatory reaction | Induces milder immune suppression and a less pronounced inflammatory response |
| Lymphocyte modulation | Decreases T-lymphocyte activity and antibody production by B-lymphocytes; weaker response to pathogens, increased risk of infections | More gradual Th1/Th2 transition; less suppression of immune cells |
| Antigen-presenting cells | Decreases macrophage and dendritic cell activity, resulting in reduced T-cell activation | Local anesthetics may modulate macrophage and monocyte activity and surface molecule expression |
| Neutrophils and phagocytosis | Decreases migration and phagocytic activity of neutrophils; reduced ability to fight infection | Better preservation of innate immune cell function |
| NK cells | Decreases NK cell activity; potential facilitation of infection or tumor spread | Preserves NK cell cytotoxic function compared with general anesthesia |
| Intestinal barrier integrity | Increases intestinal permeability; risk of microbiota imbalance, bacterial translocation, and risk of hospital-acquired infections | No significant disruption of intestinal barrier function reported |
| Postoperative immunity | Broad suppression of postoperative immune function | Better preservation of immune competence, particularly in cancer and immunocompromised patients |
| Oncologic implications | May enhance tumor dissemination and angiogenesis through immune suppression | May reduce perioperative tumor cell spread, angiogenesis and immune suppression during the perioperative period |
| Clinical outcomes | Associated with a higher risk of infection and a possible increase in tumor recurrence | No conclusive evidence of reduced tumor recurrence; available studies remain limited and biased |
| Research limitations | Moderate-quality evidence indicating immunosuppression | Data is mostly retrospective, with small sample sizes, inconsistent outcomes, low quality, and a high risk of bias |
| Recommendation | Use cautiously in immunocompromised or oncologic settings | Further randomized controlled trials needed; anesthetic choice should be individualized |
| Source: own. HPA – hypothalamic-pituitary-adrenal; IL-6 – interleukin 6; NK – natural killer; TNF-α – tumor necrosis factor α; IL-1β – interleukin 1β; IL-10 – interleukin 10; Th1 – T helper 1 cells; Th2 – T helper 2 cells. | ||