Intrathecal application of the antimicrobial peptide CRAMP reduced mortality and neuroinflammation in an experimental model of pneumococcal meningitis. Issue 2 (August 2015)

• Record Type: Journal Article
• Authors: Dörr, Arndt; Kress, Eugenia; Podschun, Rainer; Pufe, Thomas; Tauber, Simone C.; Brandenburg, Lars-Ove
• Is Part Of: Journal of infection. Volume 71:Issue 2(2015)
• Page Start: 188
• Page End: 199
• Publication Date: 2015-08
• Subjects: Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2015.04.006
• Languages: English
• ISSNs: 0163-4453

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Summary</title> <sec> <p id="abspara0010">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.</p> <p id="abspara0015">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.</p> <p id="abspara0020">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.</p> </sec> </abstract>