Anti-IL-6 Neutralizing Antibody Modulates Blood-brain Barrier Function in the Ovine Fetus

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2015 Jan 23

PMID 25609424

Citations 45

Authors

Jiyong Zhang

Grazyna B Sadowska

Xiaodi Chen

Seon Yeong Park

Jeong-Eun Kim

Courtney A Bodge

Erin Cummings

Yow-Pin Lim

Oleksandr Makeyev

Walter G Besio

John Gaitanis

William A Banks

Barbara S Stonestreet

Affiliations

Soon will be listed here.

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.

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