The Effect of rFVIIa on Pro- and Anti-Inflamatory Cytokines in Serum and Cerebrospinal Fluid in a Swine Model of Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is associated with significant infectious and inflammatory complications. Though increasing evidence suggests that rFVIIa administration may be efficacious for the pre-hospital treatment of TBI, the FVIIa-tissue factor complex has been shown to be immunologically active. To date the cytokine response to rFVlla administration for the treatment of TBI has not been evaluated. Twenty anesthetized immature Yorkshire swine underwent fluid percussion TBI. At 15 min following injury, animals were randomized to receive either 90 micrograms//kg rFVIla (rFVlla) or nothing. Animals were observed for 6 h and then euthanized. Plasma and cerebrospinal (CSF) samples were collected at 0 min and 360 min, and ELISA analysis of TNF-alpha, IL-l beta and lL-10 was performed. SuJVival in both groups was 100%. Baseline cytokine concentrations were not statistically different between rFVlla and control animals in plasma or CSF. Animals in both groups did not have significant changes in plasma cytokine concentrations following TBI. Control animals did not demonstrate significant changes from baseline of CSF cytokine concentrations following TBI. The administration of rFVIIa however, resulted in significant increases in CSF TNF-alpha concentration (232.0 pg/ml +/- 75.9 vs 36.4 pg/ml +/- 10.4, p = 0.036) and lL-10 concentration ( 10.7 pg/ml +/- 0.6 vs 8.8 pg/ml +/- 0.1, p = 0.015). lL-1beta concentrations were not significantly changed over the experimental time course. These results suggest that rFVIIa administration for the treatment of TBI is not immunologically inert, and is associated with increased CSF concentrations of TNF-alpha and IL-10.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2011
Accession Number
ADA552240

Entities

People

  • Anke Scultetus
  • Bobby Kim
  • Charles Auker
  • Daniel Freilich
  • Daniel Solomon
  • Françoise Arnaud
  • Richard Mccarron

Organizations

  • Naval Medical Research Center

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Biomedical Research
  • Blood
  • Blood Coagulation Factors
  • Blood-Brain Barrier
  • Brain
  • Brain Injuries
  • Cardiovascular Physiological Phenomena
  • Cytokines
  • Health Services
  • Hemorrhage
  • Hospitals
  • Laboratory Animals
  • Proteins
  • Surgery
  • Veins
  • Wounds And Injuries

Fields of Study

  • Medicine

Readers

  • Gulf War Illness and Chronic Multisymptom Illness in Veterans.
  • Neurotrauma and Rehabilitation Medicine.
  • Toxicology/Environmental Toxicology