Infarct volume is a major determiner of post-stroke immune cell function and susceptibility to infection.
OBJECTIVE
Acute ischemic stroke in humans is associated with profound alterations in the immune system. Hallmarks of this stroke-induced immunodepression syndrome are: lymphocytopenia, impairment of T helper cell and monocyte function. We studied which stroke-specific factors predict these immunologic alterations and subsequent infections.


METHODS
Leukocyte/lymphocyte subsets were assessed serially by white blood cell count and fluorescence-activated cell sorter analysis in ischemic stroke patients (n=50) at baseline, day 1, and day 4 after stroke onset and compared to an age-matched control group (n=40). Concomitantly, monocytic human leukocyte antigen-DR expression and the in vitro function of blood monocytes measured by the production of tumor necrosis factor-alpha upon stimulation with lipopolysaccharide were assessed. Associations of these immunologic parameters with stroke specific factors (National Institutes of Health Stroke Scale, infarct size) were explored. Multivariable logistic regression analysis was applied to identify early predictors for poststroke respiratory and urinary tract infections.


RESULTS
Infarct volume was the main factor associated with lymphocytopenia on day 1 and day 4 poststroke. Particularly, blood natural killer cell counts were reduced after stroke. Monocyte counts increased after ischemia paralleled by a profound deactivation predominantly after extensive infarcts. Reduced T helper cell counts, monocytic human leukocyte antigen-DR expression, and monocytic in vitro production of tumor necrosis factor-alpha were associated with infections in univariate analyses. However, only stroke volume prevailed as independent early predictor for respiratory infections (OR 1.03; CI 1.01 to 1.04).


CONCLUSIONS
Infarct volume determines the extent of lymphocytopenia, monocyte dysfunction, and is a main predictor for subsequent infections.
Hug
Andreas
A
Department of Neurology, University of Heidelberg, University Hospital Heidelberg, Germany. andreas.hug@med.uni-heidelberg.de
Dalpke
Alexander
A
Wieczorek
Nina
N
Giese
Thomas
T
Lorenz
Alexander
A
Auffarth
Gerd
G
Liesz
Arthur
A
Veltkamp
Roland
R
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D020520:Brain Infarction / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007239:Infections / Q000276:immunology*; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D020127:Recovery of Function / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha