The immune system serves as the body's primary defense mechanism against pathogens and disease. Medications administered in the perioperative setting can either support or impair immune function, making it important to understand these effects in the context of the physiological stress of surgical procedures.
The immune system is broadly divided into innate immunity, which provides rapid non-specific responses through anatomic barriers, humoral responses, and cellular immunity including macrophages, monocytes, neutrophils, and natural killer (NK) cells; and adaptive immunity, mediated by T and B lymphocytes that create immunological memory for long-term defense.
Perioperative adjuvants — such as benzodiazepines, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs) — are medications commonly administered alongside primary anesthetic agents to enhance overall sedation, reduce preoperative anxiety, manage pain, and improve recovery. Each class exerts measurable effects on immune function.
Benzodiazepines affect the central nervous system and can influence phagocytosis, chemotaxis, and cytokine production through peripheral benzodiazepine receptors. Studies with midazolam showed dose-dependent reductions in neutrophil and macrophage oxidative burst and phagocytosis, though diazepam has demonstrated opposing effects in certain experimental contexts, highlighting the complexity of class-level generalizations.
Opioids are broadly recognized for their immunosuppressive properties, including suppression of NK cell cytotoxicity, inhibition of macrophage and neutrophil phagocytosis, and modulation of T-cell function. The clinical significance of opioid-induced immunosuppression depends on dose, duration, and the specific agent used.
NSAIDs suppress immune function by inhibiting COX-1 and COX-2 enzymes that produce prostaglandins. These drugs can prevent immunosuppressive cytokine production while also affecting tumor microenvironments in certain cancer contexts, a finding of growing clinical interest in oncologic surgery.
Both innate and adaptive immune components work together to defend against pathogens and facilitate healing. While perioperative adjuvants improve patient comfort and pain management, their impact on immune function warrants ongoing attention in research and clinical practice to minimize any negative downstream effects on recovery and resistance to infection.