Reduced ex vivo release of pro-inflammatory cytokines and elevated plasma interleukin-6 are inflammatory signatures of post-stroke delirium

Kowalska, Katarzyna; Klimiec, Elzbieta; Węglarczyk, Kazimierz; Pera, Joanna; Słowik, Agnieszka; Siedlar, Maciej; Dziedzic, Tomasz

doi:10.1186/s12974-018-1156-y

Cited by 33 publications

(28 citation statements)

References 37 publications

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“…The agerelated alterations in the GM composition include an increase of Proteobacteria, a decrease of the Firmicutes to Bacteroides, and a reduction of microbiota diversity (Vaiserman et al, 2017). The changes of GM may be associated with inflammation and endotoxin tolerance during the acute phase of stroke and myocardial infarction (Hernandez-Jimenez et al, 2017;Kowalska et al, 2018;Krishnan and Lawrence, 2019). In this study, the increased abundances of Klebsiella, Enterobacteriaceae, Enterobacteriales, Gammaproteobacteria of phylum Proteobacteria, and Prevotella were still found in age-matched PSCI patients compared with PSNCI patients.…”

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confidence: 51%

Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke

Liu

Gong

Zhang

et al. 2020

Front. Aging Neurosci.

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Post-stroke cognitive impairment (PSCI) is a common neuropsychiatric complication of stroke. Mounting evidence has demonstrated a connection between gut microbiota (GM) and neuropsychiatric disease. Our previous study revealed the changes in the GM in a mouse model of vascular dementia. However, the characteristic GM of PSCI remains unclear. This study aimed to characterize the GM of PSCI and explored the potential of GM as PSCI biomarkers. A total of 93 patients with ischemic stroke were enrolled in this study. The patients were divided into two groups according to their MoCA scores 3 months after stroke onset. Clinical data and biological variables were recorded. GM composition was analyzed using 16S ribosomal RNA sequencing, and the characteristic GM was identified by linear discriminant analysis Effect Size (Lefse). Our results showed that Proteobacteria was highly increased in the PSCI group compared with the post-stroke non-cognitive impairment (PSNCI) group, the similar alterations were also observed at the class, order, family, and genus levels of Proteobacteria. After age adjustments, the abundance of Firmicutes, and its members, including Clostridia, Clostridiales, Lachnospiraceae, and Lachnospiraceae_other, were significantly decreased in the age-matched PSCI group compared with the PSNCI group. Besides, the GM was closely associated with MoCA scores and the risk factors for PSCI, including higher baseline National Institute of Health Stroke Scale score, higher homocysteine (Hcy) level, higher prevalence of stroke recurrence, leukoaraiosis, and brain atrophy. The KEGG results showed the enriched module for folding, sorting and degradation (chaperones and folding catalysts) and the decreased modules related to metabolisms of cofactors and vitamins, amino acid, and lipid in PSCI patients. A significant correlation was observed between PSCI and the abundance of Enterobacteriaceae after adjustments (P = 0.035). Moreover, the receiver operating characteristic (ROC) models based on the characteristic GM and Enterobacteriaceae could distinguish PSCI patients from PSNCI patients [area under the curve (AUC) = 0.840, 0.629, respectively]. Our findings demonstrated that the characteristic GM, especially Enterobacteriaceae, might have the ability to predict PSCI in post-stroke patients, which are expected to be used as clinical biomarkers of PSCI.

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Section: Figure 3 |mentioning

confidence: 51%

Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke

Liu

Gong

Zhang

et al. 2020

Front. Aging Neurosci.

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“…In our analyses, Mon1 and Mon2 correlated with IL6 levels before surgery. Other studies could show that patients with delirium hat significant higher blood cytokine levels (including IL6) comparing to those without delirium 35 . On the other hand, IL6 mediated neutrophil activation is one of the central mechanisms in AKI 36 .…”

Section: Discussionmentioning

confidence: 96%

Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

Mossanen

Jansen

Pracht

et al. 2020

Sci Rep

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Elective cardiac surgery has low procedural complications. However, about 40% of patients develop extracardiac complications including delirium and acute kidney injury. We hypothesized that inflammatory processes and immune cell activation might be associated with these complications. We therefore prospectively included 104 patients undergoing cardiac surgery in our study. We assessed peripheral blood leukocyte populations by flow cytometry and circulating cytokines before operation, after surgery and at days one and four post-operatively. Patients undergoing cardiac surgery showed significantly elevated leukocytes and neutrophils after surgery. On the contrary, monocytes decreased after surgery and significantly increased at days 1 and 4, particularly classical (Mon1,CD14++CD16−) and intermediate (Mon2,CD14++CD16+) monocytes. While peripheral leukocyte subsets were unaltered in patients with infectious (n = 15) or cardiac complications (n = 31), post-operative leukocytes (p = 0.0016), neutrophils (p = 0.0061) and Mon2 (p = 0.0007) were clearly raised in patients developing extracardiac complications (n = 35). Using multiple logistic regression analyses, patient's age, ICU days, number of blood transfusions and elevated post-surgery Mon2 independently predicted extracardiac complications. Our findings demonstrate that elevated Mon2 after cardiac surgery are associated with an increased risk for extracardiac complications. These findings might improve the risk estimation after cardiac operations and the role of Mon2 for inflammation in cardiac surgery.Despite advances in surgical and anesthetic techniques as well as enhanced postoperative care, cardiac surgery is still associated with a high risk of postoperative complications 1 . Besides typical cardiac (e.g., arrhythmia, myocardial infarction) and infectious complications (e.g., wound infection, pneumonia and sepsis), extracardiac non-infectious complications like acute kidney injury (AKI, 30%) and delirium (up to 26-52%) are frequent in patients after cardiac surgery 2,3 . It has been speculated that a large part of these complications could be explained by excessive inflammation caused by extracorporeal cardio-pulmonary bypass (CPB), hypothermia, myocardial ischemia and reperfusion and tissue damage due to the surgical procedure 4,5 . The influence of distinct immune cells and their subpopulations on the occurrence of post-operative complications is still ambiguous and needs further investigations. Particularly monocytes seems to play in important role within this context 6,7 .Circulating monocyte subsets represent a continuum of differentiation stages 8,9 . Using the surface markers CD14 (LPS receptor) and CD16 (FcγRIII), blood monocytes can be subdivided into three subpopulations, CD14++CD16− "classical" monocytes (Mon1), CD14++CD16+ "intermediate" (Mon2) and CD14-16+

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“…As expected, monocyte counts were positively correlated with Uninhibited TNF‐α (ie, the top of the dose‐response curve) because this value represents the production of TNF‐α in the absence of the inhibitory influence of dexamethasone. Prior ex vivo studies often express TNF‐α as a ratio per the number of monocytes, implying that monocytes are the sole source of ex vivo production of TNF‐α and that there is a direct one‐to‐one relationship between TNF production and monocyte number 39‐41 . However, in African American women's early pregnancy, we found that the number of monocytes could only explain 14% of the interindividual variation in TNF‐α production in the absence of glucocorticoids to suppress the immune response.…”

Section: Discussionmentioning

confidence: 63%

Glucocorticoid receptor sensitivity in early pregnancy in an African American cohort

Clarke

Corwin

Dunlop

et al. 2020

American J Rep Immunol

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Problem Disruption in homeostatic feedback loops between inflammatory mediators and the hypothalamic‐pituitary‐adrenal (HPA) axis is a key mechanism linking chronic stress to inflammation and adverse health outcomes, including those occurring during pregnancy. In particular, alterations in glucocorticoid sensitivity may occur as a result of chronic stress, including that due to racial discrimination, and may be implicated in the persistent adverse maternal and infant health outcomes experienced by African Americans. While there are a few large‐scale studies in human pregnancy that measure both cytokines and HPA axis hormones, to our knowledge, none directly measure glucocorticoid sensitivity at the cellular level, especially in an African American population. Method of study We measured the full range of the dexamethasone (DEX) dose‐response suppression of TNF‐α in first‐trimester blood samples from 408 African American women and estimated leukocyte cell type contribution to the production of TNF‐α. Results The mean (SD) DEX level needed to inhibit TNF‐α production by 50% (ie, DEX IC50) was 9.8 (5.8) nmol/L. Monocytes appeared to be the main driver of Uninhibited TNF‐α production, but monocyte counts explained only 14% of the variation. Monocyte counts were only weakly correlated with the DEX IC50 (r = −.11, P < .05). Moreover, there was no statistically significant correlation between the DEX IC50 and circulating pro‐inflammatory (CRP, IL‐6, IFN‐γ) or anti‐inflammatory (IL‐10) mediators (P > .05). Conclusion These findings challenge some prior assumptions and position this comprehensive study of glucocorticoid sensitivity as an important anchor point in the growing recognition of interindividual variation in maternal HPA axis regulation and inflammatory responses.

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Reduced ex vivo release of pro-inflammatory cytokines and elevated plasma interleukin-6 are inflammatory signatures of post-stroke delirium

Cited by 33 publications

References 37 publications

Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke

Gut Microbiome Signatures Are Biomarkers for Cognitive Impairment in Patients With Ischemic Stroke

Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

Glucocorticoid receptor sensitivity in early pregnancy in an African American cohort

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