Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy.

Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection. Pneumonia and urinary tract infection are the most common complications occurring in patients after stroke. The mechanisms involved in lung-brain interactions are still unknown, but some studies have suggested that inhibition of the cholinergic anti-inflammatory pathway and release of glucocorticoids, catecholamines, and damage-associated molecular patterns (DAMPs) are among the pathophysiological mechanisms involved in communication from the ischemic brain to the lungs after stroke. This review describes the modifications in local and systemic immunity that occur after stroke, outlines mechanisms of stroke-induced immunosuppression and their role in pneumonia, and highlights potential therapeutic targets to reduce post-stroke complications. Despite significant advances towards a better understanding of the pathophysiology of ischemic stroke-induced immunosuppression and stroke-associated pneumonia (SAP) in recent years, many unanswered questions remain. The true incidence and outcomes of SAP, especially in intensive care unit settings, have yet to be determined, as has the full extent of stroke-induced immunosuppression and its clinical implications.

Immunomodulatory effects of anesthetic agents in perioperative medicine.

Anesthetics comprise a heterogeneous group of drugs with multiple functions and mechanisms of action, which are not yet fully elucidated. In the clinical setting, it is difficult to isolate the effects of anesthetic agents from those of surgical stress itself or of other individual covariates. For this reason, several methods involving human immune cells and animal models have been used to study the effects of anesthetic agents on the immune system. The immunomodulation caused by anesthetic agents may lead to distinct consequences: suppression of the immune response, preventing or minimizing further distal organ injury; or suppression of the host immune reaction, which can lead to unacceptably increased risk of opportunistic infections. This review discusses the perioperative inflammatory response and the immunomodulatory properties of the most commonly used anesthetic agents in the perioperative period, addressing both their effects and proposed mechanisms of action on the innate immune system, including: biochemical and cellular defenses; barriers such as the endothelium and epithelium; biological macromolecules; domain proteins; specific cell types; and molecules such as cytokines and chemokines, which coordinate the host defense process. The immunomodulatory consequences of general anesthesia are complex. Immunosuppression can lead to beneficial effects, reducing systemic and local inflammation, or negative effects, which result in increased risk of infection. Anesthesiologists should choose the most appropriate agents based on the immune status of each patient.