OBJECTIVE--To investigate the association between release of humoral inflammatory mediators in CSF and blood and alterations of cerebral blood flow in patients with bacterial meningitis. METHODS--Immunomodulatory (interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF alpha)) and vasoactive (thromboxane A, prostacyclin, endothelin-1) molecules of probable or confirmed leucocyte origin were determined in CSF and venous blood from 20 patients with bacterial meningitis, and matched control subjects. Their concentrations were related to the presence of increased blood flow velocities in the middle cerebral arteries, as recorded by transcranial Doppler sonography. RESULTS--Concentrations of proinflammatory cytokines and prostacyclin and leucocyte counts were significantly increased in meningitis, but concentrations of the vasoconstrictors thromboxane and endothelin-1 were not. Patients with high blood flow velocities ( > 140 cm/s) had significantly increased concentrations of IL-1 beta and IL-6 and raised cell counts in CSF. CONCLUSION--The increases of key mediators of inflammation and immunoactivation and of leucocyte count in the CSF of patients with high cerebral blood flow velocities suggest a role of excessive compartmentalised host defence in pathogenesis of disorders of cerebral blood flow in bacterial meningitis.
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