Permeation of blood-borne IL15 across the blood-brain barrier and the effect of LPS.
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.
Pan
Weihong
W
Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. weihong.pan@pbrc.edu
Hsuchou
Hung
H
Yu
Chuanhui
C
Kastin
Abba J
AJ
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000503:physiopathology; D002536:Cerebral Arteries / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D019409:Interleukin-15 / Q000097:blood* / Q000276:immunology / Q000493:pharmacokinetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D018836:Inflammation Mediators; D019409:Interleukin-15; D008070:Lipopolysaccharides