ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus.
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Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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49citing papers in PubMed, 1 pooled it
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- A case-based systematic review on the SARS-COVID-2-associated cerebrovascular diseases and the possible virus routes of entry.Journal of neurovirology · 2021Pooled it
- Strategies for blood-brain barrier rejuvenation and repair.Nature reviews. Drug discovery · 2026Review
- Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction.International journal of molecular sciences · 2025Review
- Protective effects of sesamol against cigarette smoke toxicity on the blood-brain barrier.BMC complementary medicine and therapies · 2025Article
- Extracellular vesicles released by ALL patients contain HNE-adducted proteins: Implications of collateral damage.Free radical biology & medicine · 2025Article
- Blood-brain barrier permeability increases with the differentiation of glioblastoma cells in vitro.Fluids and barriers of the CNS · 2024Article
- Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagyWorld journal of diabetes · 2024Article
- Diving into the proteomic atlas of SARS-CoV-2 infected cells.Scientific reports · 2024Article
- Cytokines, Vascular Endothelial Growth Factors, and PlGF in Autoimmunity: Insights From Rheumatoid Arthritis to Multiple Sclerosis.Immune network · 2024Review
- Interleukin-6 in Traumatic Brain Injury: A Janus-Faced Player in Damage and Repair.Journal of neurotrauma · 2023Review
- The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease.Nature communications · 2023Article
- Inter-Alpha Inhibitor Proteins Modify the Microvasculature after Exposure to Hypoxia-Ischemia and Hypoxia in Neonatal Rats.International journal of molecular sciences · 2023Article
- A novel co-culture model for investigation of the effects of LPS-induced macrophage-derived cytokines on brain endothelial cells.PloS one · 2023Article
- Interleukin 6: at the interface of human health and disease.Frontiers in immunology · 2023Review
- Current Update on Transcellular Brain Drug Delivery.Pharmaceutics · 2022Review
- The Crosstalk between the Blood-Brain Barrier Dysfunction and Neuroinflammation after General Anaesthesia.Current issues in molecular biology · 2022Review
- Role of aging in Blood-Brain Barrier dysfunction and susceptibility to SARS-CoV-2 infection: impacts on neurological symptoms of COVID-19.Fluids and barriers of the CNS · 2022Review
- Activation of NLRP3 Is Required for a Functional and Beneficial Microglia Response after Brain Trauma.Pharmaceutics · 2022Article
- The association ofFrontiers in neurology · 2022Article
- Anti-IL-6 therapies in central nervous system inflammatory demyelinating diseases.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Jiyong Zhang*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Grazyna B Sadowska*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Xiaodi Chen*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Seon Yeong Park*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Jeong-Eun Kim*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Courtney A Bodge*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Erin Cummings*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Yow-Pin Lim*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Oleksandr Makeyev*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Walter G Besio*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
John Gaitanis*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
William A Banks*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Barbara S Stonestreet*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA bstonestreet@wihri.org.
Brown University · USWomen & Infants Hospital of Rhode Island · USUniversity of Rhode Island · USProThera Biologics (United States) · USVA Puget Sound Health Care System · US
Funding
UNDERGRADUATE RESEARCH AND SEMINARSP20RR016457 · NCRR · UNIVERSITY OF RHODE ISLAND · PI MARSTON, MARCIA · 2001 to 2011
$35.5MUTERINE NK CELL HOMING FROM THE PERIPHERAL CIRCULATIONP20RR018728 · NCRR · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI LAI, ZHONGBIN · 2003 to 2011
$16.7MCytokines and the blood-brain barrier in the ovine fetusR01HD057100 · NICHD · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI STONESTREET, BARBARA S · 2008 to 2020
$3.8MCOBRE for Perinatal BiologyP20GM103537 · NIGMS · WOMEN AND INFANTS HOSPITAL-RHODE ISLAND · PI PADBURY, JAMES F · 2012 to 2012
$2.1MNCRR NIH HHS P20 RR016457NCRR NIH HHS P20RR016457-11NCRR NIH HHS P20 RR018728NICHD NIH HHS 1R01-HD-057100NICHD NIH HHS R01 HD057100NIGMS NIH HHS P20 GM103537NIGMS NIH HHS P20GM103537
Abstract
Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti-IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti-IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti-IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.
Indexed as
Interleukin-6 InhibitorsAnimalsAntibodies, MonoclonalAntibodies, NeutralizingBlood-Brain BarrierBlotting, WesternBrain IschemiaCarrier ProteinsCell Membrane PermeabilityFemaleFetusInterleukin-6Membrane ProteinsPregnancyReperfusion InjurySheepAntibodies, MonoclonalAntibodies, NeutralizingCarrier ProteinsInterleukin-6Interleukin-6 InhibitorsMembrane ProteinsPlvap protein, mouseTight Junction Proteinsdevelopmentischemiamonoclonalpermeabilitytight junction proteins
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