Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood-brain barrier dysfunction and nerve growth factor production.
Interleukin (IL) 8 was measured in CSF of 14 patients with severe traumatic brain injury. IL-8 levels were significantly higher in CSF (up to 8,000 pg/ml) than serum (up to 2,400 pg/ml) (p < 0.05), suggesting intrathecal production. Maximal IL-8 values in CSF correlated with a severe dysfunction of the blood-brain barrier. Nerve growth factor (NGF) was detected in CSF of 7 of 14 patients (range of maximal NGF: 62-12,130 pg/ml). IL-8 concentrations were significantly higher in these patients than in those without NGF (p < 0.01). CSF containing high IL-8 (3,800-7,900 pg/ml) induced greater NGF production in cultured astrocytes (202-434 pg/ml) than samples with low IL-8 (600-1,000 pg/ml), which showed a smaller NGF increase (0-165 pg/ml). Anti-IL-8 antibodies strongly reduced (52-100%) the release of NGF in the group of high IL-8, whereas in the group with low IL-8, this effect was lower (0-52%). The inability of anti-IL-8 antibodies to inhibit the synthesis of NGF completely may depend on cytokines like tumor necrosis factor alpha and IL-6 found in these CSF samples, which may act in association with IL-8. Thus, IL-8 may represent a pivotal cytokine in the pathology of brain injury.
Kossmann
T
T
Division of Trauma Surgery, University of Zürich Medical School, Switzerland.
Stahel
P F
PF
Lenzlinger
P M
PM
Redl
H
H
Dubs
R W
RW
Trentz
O
O
Schlag
G
G
Morganti-Kossmann
M C
MC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000097:blood / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D002478:Cells, Cultured; D002556:Cerebrospinal Fluid Proteins / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000097:blood / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology
D002556:Cerebrospinal Fluid Proteins; D016209:Interleukin-8; D009414:Nerve Growth Factors; D011994:Recombinant Proteins