Cerebral output of cytokines in patients with pneumococcal meningitis.
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.
Møller
Kirsten
K
Departments of Infectious Diseases, University Hospital Rigshospitalet, Copenhagen, Denmark. kristen.moller@dadlnet.dk
Tofteng
Flemming
F
Qvist
Tavs
T
Sahl
Christian
C
Sønderkaer
Signe
S
Pedersen
Bente K
BK
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
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha