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

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-1beta 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 inflammation.

• Authors: 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
• Journal: The American journal of pathology (Am J Pathol) Vol. 171 Issue 4 Pg. 1199-214 (Oct 2007) ISSN: 0002-9440 [Print] United States
• PMID: 17717149 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Bacterial Agents
• Chemokine CCL2
• Interleukin-1beta
• Tlr2 protein, mouse
• Toll-Like Receptor 2
• Minocycline

Topics

• Animals
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Brain Abscess (drug therapy, immunology, pathology)
• Chemokine CCL2 (metabolism)
• Encephalitis (drug therapy, immunology, microbiology)
• Interleukin-1beta (metabolism)
• Mice
• Mice, Inbred C57BL
• Minocycline (pharmacology, therapeutic use)
• Neuroglia (drug effects, immunology)
• Staphylococcal Infections (drug therapy, immunology)
• Staphylococcus aureus (drug effects)
• Toll-Like Receptor 2 (antagonists & inhibitors, metabolism)