Permeation of blood-borne IL15 across the blood-brain barrier and the effect of LPS

J Neurochem. 2008 Jul;106(1):313-9. doi: 10.1111/j.1471-4159.2008.05390.x. Epub 2008 Jul 1.

Abstract

Interleukin15 (IL 15) is a proinflammatory cytokine with elevated concentrations in autoimmune diseases involving the periphery (e.g. rheumatoid arthritis) and CNS (e.g. multiple sclerosis). Its interactions with the blood-brain barrier (BBB) were studied in normal and lipopolysaccharide (LPS)-treated mice. (125)I-IL15 remained intact for at least 10 min after i.v. injection and reached CNS parenchyma with regional differences between brain and spinal cord. Both in vivo and in situ brain perfusion of (125)I-IL15 showed that its permeation of the BBB was non-saturable. LPS induced a significant increase of IL15 uptake by the brain and spinal cord, partly related to a higher general permeability of the BBB. The results suggest that the BBB is an interface for blood-borne IL15 to interact with the CNS in the basal state and during inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoimmune Diseases of the Nervous System / immunology
  • Autoimmune Diseases of the Nervous System / metabolism
  • Autoimmune Diseases of the Nervous System / physiopathology
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / immunology
  • Blood-Brain Barrier / metabolism*
  • Brain / blood supply
  • Brain / immunology
  • Brain / physiopathology
  • Cerebral Arteries / drug effects
  • Cerebral Arteries / immunology
  • Cerebral Arteries / metabolism*
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / immunology
  • Encephalitis / immunology*
  • Encephalitis / physiopathology
  • Inflammation Mediators / pharmacology
  • Interleukin-15 / blood*
  • Interleukin-15 / immunology
  • Interleukin-15 / pharmacokinetics*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation / drug effects
  • Microcirculation / immunology
  • Microcirculation / metabolism

Substances

  • Inflammation Mediators
  • Interleukin-15
  • Lipopolysaccharides