Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS
Campbell, Jennifer H.
Burdo, Tricia H.
Bombardier, Jeffrey P.
Williams, Kenneth C.
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CitationCampbell, Jennifer H., Tricia H. Burdo, Patrick Autissier, Jeffrey P. Bombardier, Susan V. Westmoreland, Caroline Soulas, R. Gilberto Gonzalez, Eva-Maria Ratai, and Kenneth C. Williams. 2011. Minocycline inhibition of monocyte activation correlates with neuronal protection in SIV NeuroAIDS. PLoS ONE 6(4): e18688.
AbstractBackground: 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 (1H 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 CD14loCD16+ 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 CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV
replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS
Conclusion: 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.
Citation: Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, et al. (2011) Minocycline Inhibition of Monocyte Activation Correlates
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