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.
Highlights
Stroke associated infections (SAI) have been generally accepted to accompany the acute phase of stroke with an incidence rate of nearly 30-60%, contributing to a poor prognosis and higher mortality in stroke patients [1,2,3]
The activation of the sympathetic pathway could partly account for the specific immunological alterations found in stroke associated infection (SAI) patients including HLA-DR decrease and IL-10 increase, which both could be reversed by propranolol
Both clinical and animal studies show that a multitude of cytokines such as IL-6 and IL-10 are activated after www.impactjournals.com/oncotarget stroke, induce stroke-associated immunodepression, and greatly increase the risk of infection [8,9,10,11]
Summary
Stroke associated infections (SAI) have been generally accepted to accompany the acute phase of stroke with an incidence rate of nearly 30-60%, contributing to a poor prognosis and higher mortality in stroke patients [1,2,3]. There is still no effective biomarker(s) to predict SAI. Numerous studies have shown that a profound stroke-triggered immunodepression with significant changes in the levels of inflammatory factors leads to serious infectious complications in stroke patients [6,7]. Both clinical and animal studies show that a multitude of cytokines such as IL-6 and IL-10 are activated after www.impactjournals.com/oncotarget stroke, induce stroke-associated immunodepression, and greatly increase the risk of infection [8,9,10,11]. No specific immunological indicator has been identified for SAI, and the underlying mechanism remains poorly understood
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have