title: Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients.
abstract: Prostaglandins (PGs), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) are likely mediators of local inflammatory reactions. We measured PGE2, PGI2, IL-1 beta, and TNF concentrations in paired cerebrospinal fluid (CSF) samples (on admission, CSF1, and 18 to 30 hours later, CSF2) from 80 infants and children with bacterial meningitis. Forty patients received dexamethasone sodium (0.6 mg/kg per day in four intravenous doses) and 40 received an intravenous saline placebo. In CSF1, PGE2, PGI2, IL-1 beta, and TNF were detected in 90%, 56%, 98%, and 71% of specimens with mean (+/- SEM) concentrations of 462 +/- 65, 377 +/- 62, 1266 +/- 242, and 799 +/- 227 pg/mL, respectively. Concentrations of PGE2 correlated significantly with PGI2, IL-1 beta, TNF, and lactate and inversely correlated with glucose concentrations in the first CSF specimens. The PGE2, PGI2, IL-1 beta, and TNF were still detected in 40%, 18%, 97%, and 60%, respectively, of second CSF specimens obtained from placebo-treated patients. Compared with patients who had detectable PGI2 or TNF alpha concentrations in CSF2 specimens, those placebo-treated patients with no detectable PGI2 or TNF alpha activity in CSF2 had a lower incidence of neurological sequelae. Dexamethasone-treated patients had significantly lower PGE2, IL-1 beta, and lactate concentrations and higher glucose concentrations in CSF 18 to 30 hours later, shorter duration of fever, and a lower incidence of neurological sequelae than did placebo-treated patients.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
authors.forename: M M
authors.initials: MM
authors.lastname: Mustafa
authors.forename: O
authors.initials: O
authors.lastname: Ramilo
authors.forename: X
authors.initials: X
authors.lastname: Sáez-Llorens
authors.forename: K D
authors.initials: KD
authors.lastname: Olsen
authors.forename: R R
authors.initials: RR
authors.lastname: Magness
authors.forename: G H
authors.initials: GH
authors.lastname: McCracken
mesh_terms: D001424:Bacterial Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000134:cerebrospinal fluid*; D004311:Double-Blind Method; D011464:Epoprostenol / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000134:cerebrospinal fluid*; D008297:Male; D008581:Meningitis / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid* / Q000187:drug effects
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D011464:Epoprostenol; D015232:Dinoprostone