Abstract
To investigate whether neutrophil granulocytes’ function relates to post-stroke infections and clinical outcome after stroke, we prospectively recruited 95 patients after ischemic stroke and tested them for their microbiocidal neutrophil functions in this exploratory study. Additionally, 24 age-adjusted controls were examined regarding neutrophil function. Phagocytic capacity and the ability of the neutrophil granulocytes to produce reactive oxygen species (ROS) as well as CD11b and CD16 receptor expression profile were measured by flow cytometry at days 1, 3, 7, and 90 after symptom onset. Primary outcome was the development of an infection within the first week after stroke. Results of neutrophil functional measurements were compared between patients with and without infection as well as between all stroke patients and controls. Further risk factors for the development of infections were summarized in an infection-risk score for the purpose of multivariate statistical analysis. The ROS production in neutrophils after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) was reduced at baseline in patients with post-stroke infections compared to those without (p = 0.013). This difference proved to be independent from the infection-risk score in the binary logistic regression (p = 0.011). Phagocytosis and oxidative bursts were not significantly reduced in the whole stroke patient group compared to controls. Dysfunction of neutrophil granulocytes seems to play a significant role in the development of post-stroke infections. Further studies are warranted to investigate neutrophil granulocytes´ function as a potential biomarker of post-stroke infections.
Highlights
Infections—especially respiratory or urinary tract infections—are common complications after acute ischemic stroke affecting up to 30% of the patients [1,2]
There are only few and small studies dealing with the microbiocidal function of circulating neutrophil granulocytes after stroke: While reactive oxygen species (ROS) production is necessary for a successful defense against bacteria, it can reinforce inflammatory post-ischemic damage and might contribute to an unfavorable functional outcome after stroke [7,8]
Patients with infections had a more severe stroke (NIHSS at baseline and S100B at day 3; p < 0.001 and p < 0.001), had no microangiopathic strokes (p = 0.02), were more often obese (p = 0.015), showed higher Neutrophil–lymphocyte ratio (NLR) (p = 0.001), and scored higher in the infection-risk score (p < 0.001) than patients without infection. modified Rankin Scale (mRS) and/or Barthel Index (BI) at day 90 could be obtained for 87 patients
Summary
Infections—especially respiratory or urinary tract infections—are common complications after acute ischemic stroke affecting up to 30% of the patients [1,2]. Cellular immunity is impaired as monocytes are partly deactivated. This is represented by lowered HLA-DR/MHC class II expression, as well as reduced tumor necrosis factor α (TNF-α) production and reduced oxidative burst activity [3,4,5]. There are only few and small studies dealing with the microbiocidal function of circulating neutrophil granulocytes after stroke: While ROS production is necessary for a successful defense against bacteria, it can reinforce inflammatory post-ischemic damage and might contribute to an unfavorable functional outcome after stroke [7,8]. In patients with ischemic stroke, a reduced amount of intracellular myeloperoxidase (MPO), a key enzyme of neutrophil defense mechanisms, was found [10]
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