科研之友
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摘要
Intravenous immunoglobulin (IVIG) contains anti-amyloid- antibodies as well as antibodies providing immunomodulatory effects that may modify chronic inflammation in Alzheimer%26apos;s disease. Answers to important questions about IVIG transport into the central nervous system and assessments of any impact amyloid- has on this transport can be provided by in vitro models of the blood-brain barrier. In this study, amyloid-[1-42] was pre-aggregated into fibrillar or oligomeric structures, and various concentrations were incubated in the brain side of the blood-brain barrier model, followed by IVIG administration in the blood side at the therapeutically relevant concentrations of 5 and 20mg/mL. IVIG accumulated in the brain side at physiologically relevant levels, with amyloid- pre-incubation increasing IVIG accumulation. The increased transport effect was dependent on amyloid- structural form, amyloid- concentration, and IVIG dose. IVIG was found to decrease monocyte chemotactic protein-1 levels 6.5-18% when low amyloid- levels were present and increase levels 4.2-23% when high amyloid- levels were present. Therefore, the presence, concentration, and structure of amyloid- plays an important role in the effect of IVIG therapy in the brain. The mechanisms of action and transport across the blood-brain barrier (BBB) for an Alzheimer%26apos;s disease therapeutic, intravenous immunoglobulin (IVIG), remain unknown. We investigated the transport of IVIG across endothelial cell BBB monolayers pre-incubated with amyloid- peptides. We found that the concentration and structure of amyloid- plays an important role in the effect of IVIG on BBB tightening and cytokine neutralization. (Note: Figure not drawn to scale.)
- 出版日期2014-7
