title: The Th1 versus Th2 cytokine profile in cerebrospinal fluid after severe traumatic brain injury in infants and children.
abstract: OBJECTIVE: To further characterize the Th1 (proinflammatory) vs. the Th2 (antiinflammatory) cytokine profile after severe traumatic brain injury (TBI) by quantifying the ventricular cerebrospinal fluid concentrations of Th1 cytokines (interleukin [IL]-2 and IL-12) and Th2 cytokines (IL-6 and IL-12) in infants and children. DESIGN: Retrospective study. SETTING: University children's hospital. PATIENTS: Twenty-four children hospitalized with severe TBI (admission Glasgow Coma Scale score, <13) and 12 controls with negative diagnostic lumbar punctures. INTERVENTIONS: All TBI patients received standard neurointensive care, including the placement of an intraventricular catheter for continuous drainage of cerebrospinal fluid. MEASUREMENTS AND MAIN RESULTS: Ventricular cerebrospinal fluid samples (n = 105) were collected for as long as the catheters were in place (between 4 hrs and 222 hrs after TBI). Cerebrospinal fluid samples were analyzed for IL-2, IL-4, IL-6, and IL-12 concentrations by enzyme-linked immunoassay. Peak and mean IL-6 (335.7 +/- 41.4 pg/mL and 259.5 +/- 37.6 pg/mL, respectively) and IL-12 (11.4 +/- 2.2 pg/mL and 4.3 +/- 0.8 pg/mL, respectively) concentrations were increased (p <.05) in children after TBI vs. controls (2.3 +/- 0.7 pg/mL and 1.0 +/- 0.5 pg/mL) for IL-6 and IL-12, respectively. In contrast, peak and mean IL-2 and IL-4 concentrations were not increased in TBI children vs. controls. Increases in the cerebrospinal fluid concentration of IL-6 were significantly associated with admission Glasgow Coma Scale score of </=4 and age of </=4 yrs. Increases in cerebrospinal fluid IL-4 and IL-12 were associated with child abuse as an injury mechanism (both p </=.05 vs. accidental TBI). CONCLUSIONS: This study confirms that IL-6 levels are increased in cerebrospinal fluid after TBI in infants and children. It is the first report of increased IL-12 levels in cerebrospinal fluid after TBI in infants and children. Further, it is the first to report on IL-2 and IL-4 levels in pediatric or adult TBI. These data suggest that selected members of both the Th1 and Th2 cytokine families are increased as part of the endogenous inflammatory response to TBI. Finally, in that both IL-6 and IL-12 (but neither IL-2 nor IL-4) can be produced by astrocytes and/or neurons, a parenchymal source for cytokines in the brain after TBI may be critical to their production in the acute phase after TBI.
authors.affiliation: Safar Center for Resuscitation Research, Pittsburgh, PA (Drs. Adelson, Carcillo, Clark, and Kochanek, Mr. Amick, Ms. Yandora, and Ms. Janesko); the Departments of Anesthesiology and Critical Care Medicine (Drs. Clark and Kochanek), Pediatrics (Drs. Clark and Kochanek), Neurological Surgery (Dr. Adelson), Psychiatry (Dr. DeKosky), Medicine (Dr. Carlos), and the School of Public Health (Dr. Wisniewski), University of Pittsburgh, Pittsburgh, PA; Children's Hospital of Pittsburgh, Pittsburgh, PA (Drs. Adelson, Carcillo, Clark, and Kochanek), and the Departments of Pediatrics and Critical Care Medicine, Children's National Medical Center, Washington, DC (Dr. Bell). E-mail: kochanekpm@anes.upmc.edu
authors.forename: Jonathan E.
authors.initials: JE
authors.lastname: Amick
authors.forename: Kristin A.
authors.initials: KA
authors.lastname: Yandora
authors.forename: Michael J.
authors.initials: MJ
authors.lastname: Bell
authors.forename: Stephen R.
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: P. David
authors.initials: PD
authors.lastname: Adelson
authors.forename: Joseph A.
authors.initials: JA
authors.lastname: Carcillo
authors.forename: Keri L.
authors.initials: KL
authors.lastname: Janesko
authors.forename: Steven T.
authors.initials: ST
authors.lastname: DeKosky
authors.forename: Timothy M.
authors.initials: TM
authors.lastname: Carlos
authors.forename: Robert S.B.
authors.initials: RS
authors.lastname: Clark
authors.forename: Patrick M.
authors.initials: PM
authors.lastname: Kochanek