A critical overview of the influence of inflammation and infection on P-glycoprotein expression and activity in the brain

Abstract

Background: P-glycoprotein is a blood–brain barrier efflux transporter that limits drug accumulation in the brain. Objective: To review recent in vivo and in vitro investigations that examined the influence of inflammation, infection and related clinical neuroinflammatory disorders on P-glycoprotein expression and activity in the brain. Methods: Critical overview of English-language studies. Results/conclusions: Inflammation and infection produce dynamic changes in P-glycoprotein expression and activity in the blood–brain barrier. In vitro, blood–brain barrier P-glycoprotein activity is downregulated after short-term exposure to inflammatory mediators whereas its activity is upregulated following more prolonged exposure. In vivo studies in both humans and animals have linked CNS inflammation, peripheral inflammation and related clinical neuroinflammatory disorders with alterations in the expression and activity of blood–brain barrier P-glycoprotein. The direction and degree of change in P-glycoprotein activity depends on the in vivo or in vitro model examined, the cell type examined (e.g., endothelial or glial), the inflammatory mediator utilized, the anatomic site in which the inflammatory response was first generated, the time points chosen for observation and the substrates analyzed. Alterations in P-glycoprotein activity affect drug activity in the CNS and seem clinically important.

Keywords::

• blood–brain barrier
• cytokines
• inflammation
• infection
• P-glycoprotein

Acknowledgements

The work was supported by a Nova Scotia Health Research Foundation operating grant.

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