Neutralizing anti-interleukin-1β antibodies reduce ischemia-related interleukin-1β transport across the blood–brain barrier in fetal sheep
| Autor: | Yow-Pin Lim, Grazyna B. Sadowska, James F. Padbury, Xiaodi Chen, Barbara S. Stonestreet, William A. Banks, Aparna Patra, Jiyong Zhang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.drug_class medicine.medical_treatment Interleukin-1beta Ischemia Gestational Age Pharmacology Fetal Hypoxia Blood–brain barrier Monoclonal antibody Article 03 medical and health sciences 0302 clinical medicine Mediator Pregnancy medicine Animals Interleukin 6 Fetus Sheep biology business.industry General Neuroscience Antibodies Monoclonal Biological Transport medicine.disease Antibodies Neutralizing 030104 developmental biology medicine.anatomical_structure Cytokine Blood-Brain Barrier Hypoxia-Ischemia Brain Immunology biology.protein Female Antibody business 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience. 346:113-125 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2016.12.051 |
| Popis: | Hypoxic ischemic insults predispose to perinatal brain injury. Pro-inflammatory cytokines are important in the evolution of this injury. Interleukin-1β (IL-1β) is a key mediator of inflammatory responses and elevated IL-1β levels in brain correlate with adverse neurodevelopmental outcomes after brain injury. Impaired blood-brain barrier (BBB) function represents an important component of hypoxic-ischemic brain injury in the fetus. In addition, ischemia-reperfusion increases cytokine transport across the BBB of the ovine fetus. Reducing pro-inflammatory cytokine entry into brain could represent a novel approach to attenuate ischemia-related brain injury. We hypothesized that infusions of neutralizing IL-1β monoclonal antibody (mAb) reduce IL-1β transport across the BBB after ischemia in the fetus. Fetal sheep were studied 24-h after 30-min of carotid artery occlusion. Fetuses were treated with placebo- or anti-IL-1β mAb intravenously 15-min and 4-h after ischemia. Ovine IL-1β protein expressed from IL-1β pGEX-2T vectors in E. Coli BL-21 cells was produced, purified, and radiolabeled with 125I. BBB permeability was quantified using the blood-to-brain transfer constant (Ki) with 125I-radiolabeled-IL-1β. Increases in anti-IL-1β mAb were observed in the brain of the mAb-treated group (P |
| Databáze: | OpenAIRE |
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