Minocycline modulates neuroinflammation independently of its antimicrobial activity in staphylococcus aureus-induced brain abscess.
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.
Kielian
Tammy
T
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham St., Slot 846, Little Rock, AR 72205, USA. kieliantammyl@uams.edu
Esen
Nilufer
N
Liu
Shuliang
S
Phulwani
Nirmal K
NK
Syed
Mohsin M
MM
Phillips
Napoleon
N
Nishina
Koren
K
Cheung
Ambrose L
AL
Schwartzman
Joseph D
JD
Ruhe
Jorg J
JJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001922:Brain Abscess / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000276:immunology; D013211:Staphylococcus aureus / Q000187:drug effects*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism
D000900:Anti-Bacterial Agents; D018932:Chemokine CCL2; D053583:Interleukin-1beta; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D008911:Minocycline
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