title: Minocycline inhibition of monocyte activation correlates with neuronal protection in SIV neuroAIDS.
abstract: BACKGROUND
  Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline's functions are not well defined.
  
  
  METHODS
  Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy ((1)H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied.
  
  
  RESULTS
  Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14(lo)CD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/Cr (neuronal injury) and circulating CD14+CD16+ and CD14(lo)CD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation.
  
  
  CONCLUSIONS
  Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts, United States of America.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Campbell
authors.forename: Tricia H
authors.initials: TH
authors.lastname: Burdo
authors.forename: Patrick
authors.initials: P
authors.lastname: Autissier
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Bombardier
authors.forename: Susan V
authors.initials: SV
authors.lastname: Westmoreland
authors.forename: Caroline
authors.initials: C
authors.lastname: Soulas
authors.forename: R Gilberto
authors.initials: RG
authors.lastname: González
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Ratai
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Williams
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D015850:Interleukin-6 / Q000378:metabolism; D016014:Linear Models; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta / Q000821:virology; D008911:Minocycline / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D017452:Receptors, IgG / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D008911:Minocycline