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. Design: Prospective physiologic study. Setting. Multidisciplinary intensive care unit. Patients. 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). Interventions: None. Measurements and Main Results: The cerebral output, defined as the cerebral blood flow multiplied by the jugular-to-arterial concen tration difference, was measured individually for the cytokines tumor necrosis factor-α, interleukin-1β, and interieukin-6. Cerebral blood flow was measured by the Kety-Schmidt method using an infusion of Xe-133', and the concentration of individual cytokines in arterial and jugular bulb blood was measured by enzyme-linked immunosorbent assay. Compared with controls, patents exhibited elevated plasma levels of all three cytokines, particularly interleukin-6, as well as a marked cerebral output of tumor necrosis factor-α 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-α and interleukin-6, which may contribute to elevating the plasma levels of these cytokines.