Cellular Immunodepression Preceding Infectious Complications after Acute Ischemic Stroke in Humans

Abstract

Background: We have recently shown that ischemic stroke causes a stress-mediator-induced long-lasting immunodepressive state in mice. Methods: Using head magnetic resonance imaging and standardized immunoassays, we prospectively investigated whether poststroke immunodepression is also seen in humans. Results: Compared to healthy volunteers (n = 30), a rapid depression of lymphocyte counts and a functional deactivation of monocytes and T helper type 1 cells was observed in acute stroke patients (SP; n = 40). Immunodepression was more pronounced in patients with severe clinical deficit or large infarction. On admission the combination of monocytic tumor necrosis factor α release ex vivo and the National Institute of Health Stroke Scale score were the best predictors for nosocomial infection, preferentially affecting older SP. Conclusion: Our data provide evidence for an immediate suppression of cell-mediated immune responses after ischemic stroke in humans.

Temporal relationship between infective endocarditis and stroke

“…[6][7][8] Other cases of stroke that precede IE may reflect the presence of shared risk factors for both stroke and IE, such as cardiac valve surgery, or poststroke risk factors that may predispose to IE, such as poststroke immunodepression or use of central venous catheters after stroke. [20][21][22][23][24][25] The nature of our data prevents us from determining the mechanistic basis for these findings, but future analyses should aim to delineate the specific pathophysiologic processes underlying the complex relationship between IE and stroke.…”

Antigen Presentation After Stroke

“…For instance, high mobility group box-1 release from the ischemic brain induced the proliferation of bone marrow-derived suppressor cells, inhibiting the adaptive immune responses and resulting in lymphopenia and functional exhaustion of monocytes [74]. In patients with stroke, the best established features of SAI are increased levels of stress hormones and antiinflammatory cytokines like IL-10 [124][125][126][127][128][129][130][131], decreased numbers of circulating lymphocytes [129,131,132], and monocyte deactivation with reduced expression of human leukocyte antigen-antigen D related and reduced capacity to produce inflammatory cytokines [129,131].…”

Brain-Derived Antigens in Lymphoid Tissue of Patients with Acute Stroke

“…5 Immunofluorescence Two-micrometer-thick frozen tissue sections were dried, washed, and fixed in ethanol 70% for 10 min. Tissue was immersed in 0.3% Triton X-100 in PBS for 10 min, blocked with 5% normal serum for 1 h, and incubated with primary Abs overnight at 4˚C in the presence of 5% normal serum, followed by secondary Abs.…”

“…However, the importance of immunity in the pathobiology of acute stroke is increasingly recognized (3). In stroke patients, it was recently described a syndrome of stroke-induced immunodepression (SIID), characterized by a decline of circulating lymphocytes, and reduced inflammatory drive of mononuclear cells that increased the risk of nosocomial infections and influenced the mortality rate (4)(5)(6). Nonetheless, SIID is regarded as an adaptive response to limit local inflammation after acute brain damage (7), although the underlying cellular, molecular, and immunologic mechanisms, and functional consequences of SIID, are still debated (8).…”