title: Monocytes are major players in the prognosis and risk of infection after acute stroke.
abstract: OBJECTIVE
  Monocytes participate in adaptive and innate immune responses. Monocyte numbers increase in patients with stroke associated infection (SAI) or severe stroke. Whether changes in monocytes are related to specific effects, or simply mark brain damage, remains unsettled.
  
  
  METHODS
  We used flow cytometry in 45 consecutive strokes and 12 healthy controls to assess the time course of monocytes, their phenotype, and the production of cytokines after stimulation. Cortisol, TNF-alpha, IFN-gamma, and IL-10 were measured in serum and metanephrine in plasma. The effects of humoral and cellular parameters on the risk of SAI and poor outcome were tested in multivariate analyses adjusted for confounders (NIHSS score, age, and tube feeding).
  
  
  RESULTS
  Surface expression of human leukocyte antigen-DR, Toll-like receptor-2, and production of TNF-alpha in monocytes were independently associated with stroke. Distinct immune mechanisms were related with functional outcome and the risk of SAI; the signature of SAI included an increase of cortisol, metanephrine, and IL-10 in serum, and reduced production of TNF-alpha in monocytes; poor outcome was associated with increased expression of Toll-like receptor-4 in monocytes (OR, 9.61; 95% CI, 1.27-72.47). SAI did not predict poor outcome (OR, 5.63; 95% CI, 0.45-70.42; P=0.18).
  
  
  CONCLUSIONS
  In human stroke, poor outcome is associated to innate responses mediated by Toll-like receptor-4 in monocytes. SAI may result from the immunosuppressive and antiinflammatory effects of corticoids, catecholamines, IL-10, and deactivated monocytes. Early treated SAI does not contribute significantly to additional brain damage. These findings encourage the exploration of strategies aimed to inhibit Toll-like receptor-4 signaling in acute stroke.
authors.affiliation: Functional Unit of Cerebrovascular Diseases, Hospital Clínic, Barcelona, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Urra
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cervera
authors.forename: Víctor
authors.initials: V
authors.lastname: Obach
authors.forename: Núria
authors.initials: N
authors.lastname: Climent
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
authors.forename: Angel
authors.initials: A
authors.lastname: Chamorro
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D016130:Immunophenotyping; D007239:Infections / Q000453:epidemiology* / Q000276:immunology*; D008297:Male; D008676:Metanephrine / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D008676:Metanephrine; D006854:Hydrocortisone