title: Role of interleukin-6 in lipopolysaccharide-induced brain injury and behavioral dysfunction in neonatal rats.
abstract: There are increasing data in support of the hypothesis that inflammatory cytokines are involved in neonatal white matter damage. Despite extensive study of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta, the role of interleukin-6 in the development of white matter damage is largely unknown. In the present study, the role(s) of interleukin-6 in mediating lipopolysaccharide-induced brain injury and behavioral changes was investigated by the intracerebral injection of lipopolysaccharide with interleukin-6 neutralizing antibody in the 5-day-old rat brain. Brain injury was examined in brain sections at postnatal day 8 and postnatal day 21. Behavioral tests including righting reflex, wire hanging maneuver, cliff avoidance, locomotor activity, gait analysis, responses in the elevated plus-maze and passive avoidance were performed from postnatal day 3 to postnatal day 21. Changes in astroglia, microglia and oligodendrocytes were studied using immunohistochemistry in the postnatal day 21 rat brain. Our results show that interleukin-6 antibody attenuated lipopolysaccharide-induced brain lateral ventricle dilation and improved neurobehavioral performance. Interleukin-6 antibody also suppressed lipopolysaccharide-induced astrogliosis and microglial activation, and increased the number of oligodendrocytes in white matter. However, no changes of tumor necrosis factor-alpha and interleukin-1beta were detected. In contrast, no histopathological changes and glial activation were observed in rats injected with only interleukin-6. The present study indicates that the contribution to brain injury by interleukin-6 depends on its interaction with other lipopolysaccharide-induced agents and not on interleukin-6 alone.
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: L-W
authors.initials: LW
authors.lastname: Fan
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: B
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: prhodes@ped.umsmed.edu.
authors.forename: P G
authors.initials: PG
authors.lastname: Rhodes
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000008:administration & dosage; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001930:Brain Injuries / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000906:Antibodies; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha