Immunosenescence in neurocritical care

Abstract

BackgroundSeveral advanced and developing countries are now entering a superaged society, in which the percentage of elderly people exceeds 20% of the total population. In such an aging society, the number of age-related diseases such as malignant tumors, diabetes, and severe infections including sepsis is increasing, and patients with such disorders often find themselves in the ICU.Main bodyAge-related diseases are closely related to age-induced immune dysfunction, by which reductions in the efficiency and specificity of the immune system are collectively termed “immunosenescence.” The most noticeable is a decline in the antigen-specific acquired immune response. The exhaustion of T cells in elderly sepsis is related to an increase in nosocomial infections after septicemia, and even death over subacute periods. Another characteristic is that senescent cells that accumulate in body tissues over time cause chronic inflammation through the secretion of proinflammatory cytokines, termed senescence-associated secretory phenotype. Chronic inflammation associated with aging has been called “inflammaging,” and similar age-related diseases are becoming an urgent social problem.ConclusionIn neuro ICUs, several neuro-related diseases including stroke and sepsis-associated encephalopathy are related to immunosenescence and neuroinflammation in the elderly. Several advanced countries with superaged societies face the new challenge of improving the long-term prognosis of neurocritical patients.

Prolonged Reactive Oxygen Species Production following Septic Insult

“…The description of a long-lasting production of ROS by immature monocytes potentially demonstrates the durability of the immunoparalysis state. The persistence of this population likely reflects both how sepsis shapes the immune system of those individuals that survive the septic insult and how this alteration may feed back into the immunoparalysis state (e.g., ROS-mediated lymphocyte suppression) ( 26 – 28 , 38 ). In addition, the presence of these cells in both mouse models and septic patients lends credence to the diligent use of animal models in the evaluation of septic insults ( 56 ).…”

“…In addition to these intrinsic deficits of lymphocytes, extrinsic impairment is also present (e.g., capacity of endothelia to promote chemotaxis and suppression by monocyte-derived cells) ( 23 – 25 ). Notably, these impairments are also observed during “inflammaging,” wherein chronic, sterile, low-grade inflammation predisposes the host to age-related disease pathogenesis ( 26 – 28 ). The parallels between sepsis-induced and age-associated immunologic impairments suggest sepsis accelerates immunologic aging.…”

Age and Sex Influence the Hippocampal Response and Recovery Following Sepsis

“…Age is another major influential factor in the outcome of sepsis since the incidence of sepsis and the associated complications increase with advancing age [14–17]. The complications may result from dysregulation of the immune system during aging termed immunosenescence, resulting in a delayed, attenuated, and prolonged response [1,3, 18–20].…”