Lipopolysaccharide hyporesponsiveness: Protective or damaging response to the brain?

Pardon, Marie Christine

Abstract

© 2015, Editura Academiei Romane. All rights reserved. Lipopolysaccharide (LPS) endotoxins are widely used as experimental models of systemic bacterial infection and trigger robust inflammation by potently activating toll-like receptors 4 (TLR4) expressed on innate immune cells. Their ability to trigger robust neuroinflammation despite poor brain penetration can prove useful for the understanding of how inflammation induced by viral infections contributes to the pathogenesis of neurodegenerative diseases. A single LPS challenge often result in a blunted inflammatory response to subsequent stimulation by LPS and other TLR ligands, but the extent to which endotoxin tolerance occur in the brain requires further clarification. LPS is also thought to render the brain transiently resistant to subsequent brain injuries by attenuating the concomitant pro-inflammatory response. While LPS hyporesponsiveness and preconditioning are classically seen as protective mechanisms limiting the toxic effects of sustained inflammation, recent research casts doubt as to whether they have beneficial or detrimental roles on the brain and in neurodegenerative disease. These observations suggest that spatio-temporal aspects of the immune responses to LPS and the disease status are determinant factors. Endotoxin tolerance may lead to a late pro-inflammatory response with potential harmful consequences. And while reduced TLR4 signaling reduces the risk of neurodegenerative diseases, up-regulation of anti-inflammatory cytokines associated with LPS hyporesponsiveness can have deleterious consequences to the brain by inhibiting the protective phenotype of microglia, aggravating the progression of some neurodegenerative conditions such as Alzheimer’s disease. Beneficial effects of LPS preconditioning, however appear to require a stimulation of anti-inflammatory mediators rather than an attenuation of the pro-inflammatory response.

Citation

Pardon, M. C. (2015). Lipopolysaccharide hyporesponsiveness: Protective or damaging response to the brain?. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 56(3), 903-913

• Journal Article Type: Review
• Acceptance Date: Dec 1, 2015
• Publication Date: 2015
• Deposit Date: Feb 17, 2020
• Publicly Available Date: May 4, 2020
• Journal: Romanian Journal of Morphology and Embryology
• Print ISSN: 1220-0522
• Electronic ISSN: 2066-8279
• Peer Reviewed: Peer Reviewed
• Volume: 56
• Issue: 3
• Pages: 903-913
• Public URL: https://nottingham-repository.worktribe.com/output/3132199
• Publisher URL: http://www.rjme.ro/RJME/resources/files/560315903913.pdf
• Related Public URLs: http://www.rjme.ro/archive/56/3/