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 2 Effects of inhalation anesthetics on the immune system [12,16,18,20,25,26,28,32].
| Effects of inhalation anesthetics on the immune system | |
|---|---|
| Isoflurane | Inhibits GABA-A-mediated transcription of proinflammatory cytokines (TNF-α, IL-6, IL-1β) in dendritic cells and T lymphocytes |
| Suppresses NF-κB signaling | |
| Blocks Mac-1–ICAM-1 binding | |
| Sevoflurane | Exhibits proinflammatory activity in some settings |
| Reduces S100β, NOX2, NOX4 protein levels (vs propofol) | |
| Causes genotoxic stress in bronchoalveolar cells (increases 8-OH-dG) | |
| Nitrous oxide | Oxidates and inactivates vitamin B, resulting in decreases in CD4 and CD8 T cells and NK-cell activity in vitamin B deficiency |
| Enflurane | Inhibits IL-1β and TNF-α secretion from NK cells activated by tumor cells |
| Impairs overall effector-cell cytokine production | |
| Upregulates HIF-1 and MMP expression (pro-tumor remodeling) | |
| Desflurane | Along with other volatile ethers, suppresses IL-1β and TNF-α release from NK cells stimulated by tumor cells |
| May induce genotoxicity and redox imbalance | |
| Halothane | Reduces IFN-stimulated NK-cell activation in vitro and in vivo (promoting metastasis) |
| Lowers circulating NK-cell counts | |
| Modulates type I IFN response to preserve neutrophil and macrophage function | |
| Source: own. GABA-A – gamma-aminobutyric acid type A; NK – natural killer; TNF-α – tumor necrosis factor alpha; IL-6 – interleukin 6; IL-1β – interleukin 1 beta; NF-κB – nuclear factor kappa-light-chain-enhancer of activated B cells; Mac-1 – macrophage-1 antigen; ICAM-1 – intercellular adhesion molecule 1; S100β – calcium-binding protein B; NOX2 – nicotinamide adenine dinucleotide phosphate oxidase 2; NOX4 – nicotinamide adenine dinucleotide phosphate oxidase 4; 8-OHdG – 8-hydroxy-2′-deoxyguanosine; HIF-1 – hypoxia-inducible factor 1; MMP – matrix metalloproteinase; IFN – interferon. | |