title: Cerebral output of cytokines in patients with pneumococcal meningitis.
abstract: OBJECTIVE
  Patients with acute bacterial meningitis frequently develop sepsis, the hallmark of which is increased plasma cytokine levels. However, it is unknown whether the brain contributes to the intravascular accumulation of cytokines in meningitis. We measured the cerebral output of cytokines to the blood during severe pneumococcal meningitis accompanied by sepsis.
  
  
  METHODS
  Prospective physiologic study.
  
  
  METHODS
  Multidisciplinary intensive care unit.
  
  
  METHODS
  Seven patients (median age, 59; range, 26-72 years) with severe pneumococcal meningitis, as evidenced by a decreased level of consciousness and the need for mechanical ventilation, and concomitant sepsis; and seven healthy volunteers (age, 24; range, 21-29 years).
  
  
  METHODS
  None.
  
  
  RESULTS
  The cerebral output, defined as the cerebral blood flow multiplied by the jugular-to-arterial concentration difference, was measured individually for the cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6. Cerebral blood flow was measured by the Kety-Schmidt method using an infusion of Xe, and the concentration of individual cytokines in arterial and jugular bulb blood was measured by enzyme-linked immunosorbent assay. Compared with controls, patients exhibited elevated plasma levels of all three cytokines, particularly interleukin-6, as well as a marked cerebral output of tumor necrosis factor-alpha and interleukin-6. No cytokine output was found in volunteers.
  
  
  CONCLUSIONS
  Patients with pneumococcal meningitis and sepsis exhibit a cerebral output of tumor necrosis factor-alpha and interleukin-6, which may contribute to elevating the plasma levels of these cytokines.
authors.affiliation: Departments of Infectious Diseases, University Hospital Rigshospitalet, Copenhagen, Denmark. kristen.moller@dadlnet.dk
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
authors.forename: Flemming
authors.initials: F
authors.lastname: Tofteng
authors.forename: Tavs
authors.initials: T
authors.lastname: Qvist
authors.forename: Christian
authors.initials: C
authors.lastname: Sahl
authors.forename: Signe
authors.initials: S
authors.lastname: Sønderkaer
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008586:Meningitis, Pneumococcal / Q000097:blood / Q000150:complications / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000150:complications; D013687:Telencephalon / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha