Intrathecal application of the antimicrobial peptide CRAMP reduced mortality and neuroinflammation in an experimental model of pneumococcal meningitis.

Abstract	Antimicrobial peptides (AP) are important components of the innate immune system. Our previous work revealed a higher mortality rate and up-regulation of proinflammatory gene expression as well as glial cell activation in cathelicidin-related antimicrobial peptide (CRAMP)-deficient mice after bacterial meningitis. However, the influence of CRAMP application on the progression of inflammation and its impact on mortality after bacterial meningitis remains unknown. To assess the effects of continuous CRAMP exposure in the brain, C57BL/6 wildtype mice were given intracerebroventricular infusion of CRAMP to investigate the effects on mortality, glial cell activation and inflammation in a mouse model of pneumococcal meningitis using immunohistochemistry and realtime RT-PCR. Our results revealed a decrease of mortality after CRAMP infusion. The intrathecal CRAMP infusion after pneumococcal meningitis resulted in a decreased mRNA expression of pro-inflammatory cytokines, whereas the immune responses including the expression of pattern recognition receptors and chemokines were increased in bacterial meningitis. Taken together, the results support the important role of CRAMP as part of the innate immune response against pathogens in bacterial CNS infections. The APs may be a promising approach for the development of an adjuvant therapy for bacterial meningitis.
Authors	Arndt Dörr, Eugenia Kress, Rainer Podschun, Thomas Pufe, Simone C Tauber, Lars-Ove Brandenburg
Journal	The Journal of infection (J Infect) Vol. 71 Issue 2 Pg. 188-99 (Aug 2015) ISSN: 1532-2742 [Electronic] England
PMID	25896094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Chemical References	Antimicrobial Cationic Peptides Cytokines
Topics	Animals Antimicrobial Cationic Peptides (therapeutic use) Brain (pathology) Cytokines (biosynthesis) Disease Models, Animal Immunohistochemistry Male Meningitis, Pneumococcal (drug therapy) Mice, Inbred C57BL Real-Time Polymerase Chain Reaction Survival Analysis Treatment Outcome

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