Blood-Brain Barrier Damage in Patients with Bacterial Meningitis: Association with Tumor Necrosis Factor- but not Interleukin-I

Abstract

Brain damage after meningeal infection could result from impairment of cerebral endothelial cell functions and disruption of blood-brain barriers. Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) produce many of their effects by acting on endothelial cells. This study correlates levels of TNF alpha and IL-1 beta in paired cerebrospinal fluid (CSF) and serum samples with the degree of blood-brain barrier damage, as manifested by CSF to serum albumin quotient, in 48 patients with bacterial meningitis and 66 controls. CSF levels of TNF alpha and IL-1 beta in bacterial meningitis were significantly higher than in controls. Intrathecal levels of TNF alpha, but not IL-1 beta, correlated with albumin quotient (P less than .001), with degree of blood-brain barrier disruption (P less than .001), and with disease severity and indices of meningeal inflammation. Sequential CSF samples demonstrated that IL-1 beta and TNF alpha disappear from the CSF within 24 h of antibiotic treatment. Data presented here suggest that TNF alpha is related to blood-brain barrier damage in bacterial meningitis and that its effect could be dissociated from that of IL-1 beta.