title: Interleukin-1β transfer across the blood-brain barrier in the ovine fetus.
abstract: Pro-inflammatory cytokines contribute to hypoxic-ischemic brain injury. Blood-brain barrier (BBB) dysfunction represents an important component of hypoxic-ischemic brain injury in the fetus. Hypoxic-ischemic injury could accentuate systemic cytokine transfer across the fetal BBB. There has been considerable conjecture suggesting that systemic cytokines could cross the BBB during the perinatal period. Nonetheless, evidence to support this contention is sparse. We hypothesized that ischemia-reperfusion increases the transfer of systemic interleukin-1β (IL-1β) across the BBB in the fetus. Ovine fetuses at 127 days of gestation were studied 4 hours after 30 minutes of bilateral carotid artery occlusion and compared with a nonischemic group. Recombinant ovine IL-1β protein was expressed from an IL-1β pGEX-2 T vector in E. coli BL-21 cells and purified. The BBB function was quantified in 12 brain regions using a blood-to-brain transfer constant with intravenous (125)I-radiolabeled IL-1β ((125)I-IL-1β). Interleukin-1β crossed the intact BBB in nonischemic fetuses. Blood-to-brain transport of (125)I-IL-1β was higher (P<0.05) across brain regions in fetuses exposed to ischemia-reperfusion than nonischemic fetuses. We conclude that systemic IL-1β crosses the intact fetal BBB, and that ischemia-reperfusion increases transfer of this cytokine across the fetal BBB. Therefore, altered BBB function after hypoxia-ischemia facilitates entry of systemic cytokines into the brain of the fetus.
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: Grazyna B
authors.initials: GB
authors.lastname: Sadowska
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: ProThera Biologics, Inc., Providence, Rhode Island, USA.
authors.forename: Yow-Pin
authors.initials: YP
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Cummings
authors.affiliation: Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Makeyev
authors.affiliation: Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA.
authors.forename: Walter G
authors.initials: WG
authors.lastname: Besio
authors.affiliation: Department of Neurology, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gaitanis
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Padbury
authors.affiliation: Division of Gerontology and Geriatric Medicine, Department of Medicine, Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
authors.affiliation: Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Stonestreet
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism* / Q000473:pathology; D005333:Fetus / Q000378:metabolism* / Q000473:pathology; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D053583:Interleukin-1beta