title: Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation.
abstract: BACKGROUND
  Evidence 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.
  
  
  RESULTS
  SAI 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.
  
  
  METHODS
  A 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.
  
  
  CONCLUSIONS
  IL-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.
authors.affiliation: Neurologic Department, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Neurologic Department, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Fu-Ling
authors.initials: FL
authors.lastname: Yan
authors.affiliation: Public Health School of Southeast University, Nanjing, China.
authors.forename: Michael
authors.initials: M
authors.lastname: Cunningham
authors.affiliation: Neurologic Department, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Qi-Wen
authors.initials: QW
authors.lastname: Deng
authors.affiliation: Neurologic Department, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Neurologic Department, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Fang-Lan
authors.initials: FL
authors.lastname: Xing
authors.affiliation: School of Medicine, Southeast University, Nanjing, China.
authors.forename: Lu-Hang
authors.initials: LH
authors.lastname: Shi
authors.affiliation: School of Medicine, Southeast University, Nanjing, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Hu
authors.affiliation: School of Medicine, Southeast University, Nanjing, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D002460:Cell Line; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007239:Infections / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D011433:Propranolol / Q000494:pharmacology; D020521:Stroke / Q000150:complications* / Q000276:immunology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000276:immunology
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D006684:HLA-DR Antigens; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016753:Interleukin-10; D011433:Propranolol
keywords: HLA-DR; immune; infection; stroke; sympathetic pathway