Targeting the complement system in bacterial meningitis.
bacterial meningitis
complement C5a
complement system
experimental models
therapeutics
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
09
01
2019
revised:
15
05
2019
accepted:
24
05
2019
pubmed:
3
8
2019
medline:
27
5
2020
entrez:
3
8
2019
Statut:
ppublish
Résumé
Bacterial meningitis is most commonly caused by Streptococcus pneumoniae and Neisseria meningitidis and continues to pose a major public health threat. Morbidity and mortality of meningitis are driven by an uncontrolled host inflammatory response. This comprehensive update evaluates the role of the complement system in upregulating and maintaining the inflammatory response in bacterial meningitis. Genetic variation studies, complement level measurements in blood and CSF, and experimental work have together led to the identification of anaphylatoxin C5a as a promising treatment target in bacterial meningitis. In animals and patients with pneumococcal meningitis, the accumulation of neutrophils in the CSF was mainly driven by C5-derived chemotactic activity and correlated positively with disease severity and outcome. In murine pneumococcal meningitis, adjunctive treatment with C5 antibodies prevented brain damage and death. Several recently developed therapeutics target C5 conversion, C5a, or its receptor C5aR. Caution is warranted because treatment with C5 antibodies such as eculizumab also inhibits the formation of the membrane attack complex, which may result in decreased meningococcal killing and increased meningococcal disease susceptibility. The use of C5a or C5aR antagonists to specifically target the harmful anaphylatoxins-induced effects, therefore, are most promising and present opportunities for a phase 2 clinical trial.
Identifiants
pubmed: 31373605
pii: 5543074
doi: 10.1093/brain/awz222
pmc: PMC6821383
doi:
Substances chimiques
Complement C5a
80295-54-1
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3325-3337Informations de copyright
© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.
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