Alpha-tocopherol attenuates NFkappaB activation and pro-inflammatory cytokine production in brain and improves recovery from lipopolysaccharide-induced sickness behavior

J Neuroimmunol. 2005 Dec;169(1-2):97-105. doi: 10.1016/j.jneuroim.2005.08.003. Epub 2005 Sep 15.

Abstract

This study was conducted to determine if alpha-tocopherol facilitates recovery from lipopolysaccharide (LPS)-induced sickness behavior through a NFkappaB-dependent mechanism. In the first study, 3 daily intraperitoneal (i.p.) injections of alpha-tocopherol (20 mg) improved recovery from sickness behavior induced by i.p. injected LPS. Furthermore, alpha-tocopherol pretreatment attenuated LPS-activated NFkappaB and pro-inflammatory cytokine production in brain. In addition, inhibiting NFkappaB activity in the brain specifically by ICV injection of a NFkappaB decoy prior to LPS, significantly accelerated recovery from LPS-induced sickness behavior. Taken together, these data indicate alpha-tocopherol modulates sickness behavior and inflammatory cytokine production in the brain through an NFkappaB-dependent pathway.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Behavior, Animal
  • Behavioral Symptoms / chemically induced
  • Behavioral Symptoms / drug therapy*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Chemistry / drug effects
  • Chromatography, High Pressure Liquid / methods
  • Cytokines / metabolism*
  • Drug Interactions
  • Electrophoretic Mobility Shift Assay / methods
  • Enzyme Activation / drug effects
  • Enzyme-Linked Immunosorbent Assay / methods
  • Exploratory Behavior / drug effects
  • Injections, Intraventricular / methods
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Protein Serine-Threonine Kinases / metabolism*
  • Recovery of Function / drug effects*
  • alpha-Tocopherol / pharmacology
  • alpha-Tocopherol / therapeutic use*

Substances

  • Antioxidants
  • Cytokines
  • Lipopolysaccharides
  • Protein Serine-Threonine Kinases
  • NF-kappa B kinase
  • alpha-Tocopherol