Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

Abstract

BackgroundEvidence has led to the consideration of immunodepression after stroke as an important contributor to stroke associated infection (SAI). However, so far no specific immunological indicator has been identified for SAI, and the underlying mechanism remains poorly understood.ResultsSAI patients had significantly higher IL-6 and IL-10 levels and lower HLA-DR levels than no-infection patients within 48h after stroke onset. NA significantly increased IL-10 levels, reduced HLA-DR expression, and decreased IL-6 expression by increasing β-arrestin2 expression which reduced the activation of the NF-κB pathway. Propranolol reversed this effect of NA by reducing β-arrestin2 expression.Materials and MethodsA systematic search for eligible clinical studies was applied to pool the differences in peripheral cytokine levels between infection and no-infection stroke patients. The underlying mechanism behind these differences was investigated in vitro by applying norepinephrine (NA) and lipopolysaccharide (LPS) to simulate sympathetic pathway activation and sepsis respectively in THP-1 cells. Propranolol was applied to determine the effect of reversing the activation of the sympathetic pathway. Immunological indicators were also detected to assess the immune activation of THP-1 cells and measurements of the expression of β-arrestin2, NF-κB, IκBα and phosphor-IκBα were performed to assess the activation of the sympathetic pathway.ConclusionIL-6, IL-10 and HLA-DR are good candidate biomarkers for SAI. The activation of the sympathetic pathway could partly account for the specific immunological alterations found in SAI patients including HLA-DR decrease and IL-10 increase, which both could be reversed by propranolol. However, the mechanism underlying IL-6 increase still needs further exploration.

Predictors of Urinary Tract Infection in Acute Stroke Patients: A Case Control Study

“…Subsequently, the interleukin-6 will stimulate the proliferation and differentiation of cells involved in the immune response, thereby enhancing the function of these cells. Finally, through this process, interleukin-6 plays an anti-infective role (44).The results of our study found that interleukin-6 might be used for the prediction of UTI after a stroke is about the same as previous studies (16,17,29).…”

“…The incidence of urinary tract infection is about 19% (10). In addition, the occurrence of infection can further aggravate the physical damage caused by stroke, and this process will form a vicious circle with stroke (11)(12)(13)(14)(15)(16). The circle will lead to a worse clinical prognosis (7,(17)(18)(19)(20).…”

Blood Glutamate Levels Are Closely Related to Acute Lung Injury and Prognosis after Stroke

“…In this study, we also measured the levels of inflammatory markers in blood; we found that patients with ALI had much higher levels of inflammatory markers than patients without ALI (Table S1 in Supplementary Material), and additional analysis showed a positive correlation between blood glutamate levels and IL-6 levels during hospitalization (Figure S3 in Supplementary Material). After brain injury, the activation of the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis has been shown to be associated with the development of systemic inflammatory complications ( 36 , 37 ); however, it is noteworthy that in patients without ALI but who were diagnosed with a complicated chest infection, even though inflammatory mediator levels in these patients were similar to those in patients with ALI, the mean glutamate levels in these patients were much lower (Figure S2A in Supplementary Material). In addition, our previous animal experiments demonstrated that high concentrations of blood glutamate mediate interactions between the adenosine A 2A receptor and the metabotropic glutamate receptor 5 on neutrophils, thereby inducing the release of inflammatory mediators ( 14 ).…”

Predictors of urinary tract infection in acute stroke patients

“…[ 42 ] The results of our study found that interleukin-6 might be used for the prediction of UTI after a stroke is about the same as previous studies. [ 16 , 17 , 29 ]…”

“…[ 10 ] In addition, the occurrence of infection can further aggravate the physical damage caused by stroke, and this process will form a vicious circle with stroke. [ 11 – 16 ] The circle will lead to a worse clinical prognosis. [ 7 , 17 – 20 ]…”