Minocycline modulates neuroinflammation independently of its antimicrobial activity in Staphylococcus aureus-induced brain abscess

Tammy Kielian, Nilufer Esen, Shuliang Liu, Nirmal K. Phulwani, Mohsin M. Syed, Napoleon Phillips, Koren Nishina, Ambrose L. Cheung, Joseph D. Schwartzman, Jorg J. Ruhe

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Minocycline exerts beneficial immune modulatory effects in several noninfectious neurodegenerative disease models; however, its potential to influence the host immune response during central nervous system bacterial infections, such as brain abscess, has not yet been investigated. Using a minocycline-resistant strain of Staphylococcus aureus to dissect the antibiotic's bacteriostatic versus immune modulatory effects in a mouse experimental brain abscess model, we found that minocycline significantly reduced mortality rates within the first 24 hours following bacterial exposure. This protection was associated with a transient decrease in the expression of several proinflammatory mediators, including interleukin-1β and CCL2 (MCP-1). Minocycline was also capable of protecting the brain parenchyma from necrotic damage as evident by significantly smaller abscesses in minocycline-treated mice. In addition, minocycline exerted anti-inflammatory effects when administered as late as 3 days following S. aureus infection, which correlated with a significant decrease in brain abscess size. Finally, minocycline was capable of partially attenuating S. aureus-dependent microglial and astrocyte activation. Therefore, minocycline may afford additional therapeutic benefits extending beyond its antimicrobial activity for the treatment of central nervous system infectious diseases typified by a pathogenic inflammatory component through its ability to balance beneficial versus detrimental in flammation.

Original languageEnglish (US)
Pages (from-to)1199-1214
Number of pages16
JournalAmerican Journal of Pathology
Volume171
Issue number4
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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